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Rabbit anti-parvalbumin antibody

RRID:AB_10000344

Antibody ID

AB_10000344

Target Antigen

parvalbumin rat

Proper Citation

(Swant Cat# PV 25, RRID:AB_10000344)

Clonality

polyclonal antibody

Comments

This antiserum was produced against rat muscle parvalbumin (1). It cross-reacts with many other species, including human parvalbumin. It can be used in immunohistochemistry, but not for immunoblotting. This antibody replaces PV 28.

Host Organism

rabbit

Vendor

Swant

Antioxidant Treatment in Male Mice Prevents Mitochondrial and Synaptic Changes in an NMDA Receptor Dysfunction Model of Schizophrenia.

  • Phensy A
  • eNeuro
  • 2018 May 3

Literature context:


Abstract:

Glutamate theories of schizophrenia suggest that the disease is associated with a loss of NMDA receptors, specifically on GABAergic parvalbumin-expressing interneurons (PVIs), leading to changes in the excitation-inhibition balance in the prefrontal cortex (PFC). Oxidative stress contributes to the loss of PVI and the development of schizophrenia. Here, we investigated whether the glutathione precursor N-acetyl cysteine (NAC) can prevent changes in synaptic transmission at pyramidal cells and PVIs that result from developmental NMDAR blockade and how these changes are related to mitochondrial dysfunction in the PFCs of mice. Perinatal treatment with ketamine induced persistent changes in the reduced glutathione/oxidized glutathione (glutathione disulfide) ratio in the medial PFC, indicating long-lasting increases in oxidative stress. Perinatal ketamine treatment also reduced parvalbumin expression, and it induced a decline in mitochondrial membrane potential, as well as elevations in mitochondrial superoxide levels. At the level of synaptic function ketamine reduced inhibition onto layer 2/3 pyramidal cells and increased excitatory drive onto PVI, indicating long-lasting disruptions in the excitation-inhibition balance. These changes were accompanied by layer-specific alterations in NMDAR function in PVIs. All of these changes were mitigated by coadministration of NAC. In addition, NAC given only during late adolescence was also able to restore normal mitochondria function and inhibition at pyramidal cells. These results show that ketamine-induced alterations in PFC physiology correlate with cell type-specific changes in mitochondria function. The ability of NAC to prevent or restore these changes supports the usefulness of antioxidant supplementation in the treatment of schizophrenia.

Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents.

  • Tan Z
  • Neuron
  • 2018 Apr 18

Literature context:


Abstract:

Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity. Such inhibitions in the hippocampus impair both hippocampal-prefrontal synchrony and top-down attention, whereas those in the prefrontal cortex alter attention, but not synchrony. These observations identify a role of ErbB4-dependent GABA activity in the hippocampus in synchronizing the hippocampal-prefrontal pathway and demonstrate that acute, dynamic ErbB4 signaling is required to command top-down attention. Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders. VIDEO ABSTRACT.

Funding information:
  • Intramural NIH HHS - ZIA BC010632-09(United States)

Differential Expression and Cell-Type Specificity of Perineuronal Nets in Hippocampus, Medial Entorhinal Cortex, and Visual Cortex Examined in the Rat and Mouse.

  • Lensjø KK
  • eNeuro
  • 2018 Mar 28

Literature context:


Abstract:

Perineuronal nets (PNNs) are specialized extracellular matrix (ECM) structures that condense around the soma and proximal dendrites of subpopulations of neurons. Emerging evidence suggests that they are involved in regulating brain plasticity. However, the expression of PNNs varies between and within brain areas. A lack of quantitative studies describing the distribution and cell-specificity of PNNs makes it difficult to reveal the functional roles of PNNs. In the current study, we examine the distribution of PNNs and the identity of PNN-enwrapped neurons in three brain areas with different cognitive functions: the dorsal hippocampus, medial entorhinal cortex (mEC) and primary visual cortex (V1). We compared rats and mice as knowledge from these species are often intermingled. The most abundant expression of PNNs was found in the mEC and V1, while dorsal hippocampus showed strikingly low levels of PNNs, apart from dense expression in the CA2 region. In hippocampus we also found apparent species differences in expression of PNNs. While we confirm that the PNNs enwrap parvalbumin-expressing (PV+) neurons in V1, we found that they mainly colocalize with excitatory CamKII-expressing neurons in CA2. In mEC, we demonstrate that in addition to PV+ cells, the PNNs colocalize with reelin-expressing stellate cells. We also show that the maturation of PNNs in mEC coincides with the formation of grid cell pattern, while PV+ cells, unlike in other cortical areas, are present from early postnatal development. Finally, we demonstrate considerable effects on the number of PSD-95-gephyrin puncta after enzymatic removal of PNNs.

Gap Junctions Interconnect Different Subtypes of Parvalbumin-Positive Interneurons in Barrels and Septa with Connectivity Unique to Each Subtype.

  • Shigematsu N
  • Cereb. Cortex
  • 2018 Feb 27

Literature context:


Abstract:

Parvalbumin (PV)-positive interneurons form dendritic gap junctions with one another, but the connectivity among gap junction-coupled dendrites remains uninvestigated in most neocortical areas. We visualized gap junctions in layer 4 of the mouse barrel cortex and examined their structural details. PV neurons were divided into 4 types based on the location of soma and dendrites within or outside barrels. Type 1 neurons that had soma and all dendrites inside a barrel, considered most specific to single vibrissa-derived signals, unexpectedly formed gap junctions only with other types but never with each other. Type 2 neurons inside a barrel elongated dendrites outward, forming gap junctions within a column that contained the home barrel. Type 3 neurons located outside barrels established connections with all types including Type 4 neurons that were confined inside the inter-barrel septa. The majority (33/38, 86.8%) of dendritic gap junctions were within 75 μm from at least 1 of 2 paired somata. All types received vesicular glutamate transporter 2-positive axon terminals preferentially on somata and proximal dendrites, indicating the involvement of all types in thalamocortical feedforward regulation in which proximal gap junctions may also participate. These structural organizations provide a new morphological basis for regulatory mechanisms in barrel cortex.

Funding information:
  • NIDCR NIH HHS - DE14197(United States)

RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait.

  • Koch SC
  • Neuron
  • 2017 Dec 20

Literature context:


Abstract:

Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the RORβ orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid locomotor rhythm. Genetic manipulations that abrogate inhibitory RORβ IN function result in an ataxic gait characterized by exaggerated flexion movements and marked alterations to the step cycle. Inactivation of RORβ in inhibitory neurons leads to reduced presynaptic inhibition and changes to sensory-evoked reflexes, arguing that the RORβ inhibitory INs function to suppress the sensory transmission pathways that activate flexor motor reflexes and interfere with the ongoing locomotor program. VIDEO ABSTRACT.

Funding information:
  • Canadian Institutes of Health Research - AG021495(Canada)
  • NINDS NIH HHS - R01 NS080586()
  • NINDS NIH HHS - R01 NS086372()
  • NINDS NIH HHS - R01 NS090919()

Distinct Inhibitory Circuits Orchestrate Cortical beta and gamma Band Oscillations.

  • Chen G
  • Neuron
  • 2017 Dec 20

Literature context:


Abstract:

Distinct subtypes of inhibitory interneuron are known to shape diverse rhythmic activities in the cortex, but how they interact to orchestrate specific band activity remains largely unknown. By recording optogenetically tagged interneurons of specific subtypes in the primary visual cortex of behaving mice, we show that spiking of somatostatin (SOM)- and parvalbumin (PV)-expressing interneurons preferentially correlates with cortical beta and gamma band oscillations, respectively. Suppression of SOM cell spiking reduces the spontaneous low-frequency band (<30-Hz) oscillations and selectively reduces visually induced enhancement of beta oscillation. In comparison, suppressing PV cell activity elevates the synchronization of spontaneous activity across a broad frequency range and further precludes visually induced changes in beta and gamma oscillations. Rhythmic activation of SOM and PV cells in the local circuit entrains resonant activity in the narrow 5- to 30-Hz band and the wide 20- to 80-Hz band, respectively. Together, these findings reveal differential and cooperative roles of SOM and PV inhibitory neurons in orchestrating specific cortical oscillations.

Funding information:
  • NCRR NIH HHS - P51RR165(United States)

Sex- and Estrus-Dependent Differences in Rat Basolateral Amygdala.

  • Blume SR
  • J. Neurosci.
  • 2017 Nov 1

Literature context:


Abstract:

Depression and anxiety are diagnosed almost twice as often in women, and the symptomology differs in men and women and is sensitive to sex hormones. The basolateral amygdala (BLA) contributes to emotion-related behaviors that differ between males and females and across the reproductive cycle. This hints at sex- or estrus-dependent features of BLA function, about which very little is known. The purpose of this study was to test whether there are sex differences or estrous cyclicity in rat BLA physiology and to determine their mechanistic correlates. We found substantial sex differences in the activity of neurons in lateral nuclei (LAT) and basal nuclei (BA) of the BLA that were associated with greater excitatory synaptic input in females. We also found strong differences in the activity of LAT and BA neurons across the estrous cycle. These differences were associated with a shift in the inhibition-excitation balance such that LAT had relatively greater inhibition during proestrus which paralleled more rapid cued fear extinction. In contrast, BA had relatively greater inhibition during diestrus that paralleled more rapid contextual fear extinction. These results are the first to demonstrate sex differences in BLA neuronal activity and the impact of estrous cyclicity on these measures. The shift between LAT and BA predominance across the estrous cycle provides a simple construct for understanding the effects of the estrous cycle on BLA-dependent behaviors. These results provide a novel framework to understand the cyclicity of emotional memory and highlight the importance of considering ovarian cycle when studying the BLA of females.SIGNIFICANCE STATEMENT There are differences in emotional responses and many psychiatric symptoms between males and females. This may point to sex differences in limbic brain regions. Here we demonstrate sex differences in neuronal activity in one key limbic region, the basolateral amygdala (BLA), whose activity fluctuates across the estrous cycle due to a shift in the balance of inhibition and excitation across two BLA regions, the lateral and basal nuclei. By uncovering this push-pull shift between lateral and basal nuclei, these results help to explain disparate findings about the effects of biological sex and estrous cyclicity on emotion and provide a framework for understanding fluctuations in emotional memory and psychiatric symptoms.

Funding information:
  • NIDDK NIH HHS - U01 DK82223(United States)
  • NIMH NIH HHS - R01 MH084970()
  • NIMH NIH HHS - R01 MH100536()

Behavioral and stereological characterization of Hdc KO mice: Relation to Tourette syndrome.

  • Abdurakhmanova S
  • J. Comp. Neurol.
  • 2017 Nov 1

Literature context:


Abstract:

A premature termination codon in the human histidine decarboxylase (Hdc) gene has been identified in a family suffering from Guilles de la Tourette syndrome (GTS). In the current study we investigated if mice lacking the histamine producing enzyme HDC share the morphological and cytological phenotype with GTS patients by using magnetic resonance (MRI) and diffusion tensor imaging (DTI), unbiased stereology and immunohistochemistry. Behavior of Hdc knock-out (Hdc KO) mice was assessed in an open field test. The results of stereological, volumetric and DTI analysis measurements showed no significant differences between control and Hdc KO mice. The numbers and distribution of GABAergic parvalbumin or nitric oxide-expressing and cholinergic interneurons were normal in Hdc KO mice. Cortical morphology and layering in adult Hdc KO mice were also preserved. In open field test Hdc KO mice showed impaired exploratory activity and habituation when introduced to novel environment. Our results indicate that Hdc deficiency in mice does not disturb the development of striatal and cortical interneurons and does not lead to the morphological and cytological phenotypes characterized by humans with GTS. Nevertheless, histamine deficiency leads to behavioral alterations probably due to neurotransmitter dysbalance on the level of the striatum.

Funding information:
  • NIGMS NIH HHS - T32 GM008433(United States)

Seizure frequency correlates with loss of dentate gyrus GABAergic neurons in a mouse model of temporal lobe epilepsy.

  • Buckmaster PS
  • J. Comp. Neurol.
  • 2017 Aug 1

Literature context:


Abstract:

Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. This study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31-61 days earlier were video-monitored for spontaneous, convulsive seizures 9 hr/day every day for 24-36 days. Over 4,060 seizures were observed. Seizure frequency ranged from an average of one every 3.6 days to one every 2.1 hr. Hippocampal sections were processed for Nissl stain, Prox1-immunocytochemistry, GluR2-immunocytochemistry, Timm stain, glial fibrillary acidic protein-immunocytochemistry, glutamic acid decarboxylase in situ hybridization, and parvalbumin-immunocytochemistry. Stereological methods were used to measure hilar ectopic granule cells, mossy cells, mossy fiber sprouting, astrogliosis, and GABAergic interneurons. Seizure frequency was not significantly correlated with the generation of hilar ectopic granule cells, the number of mossy cells, the extent of mossy fiber sprouting, the extent of astrogliosis, or the number of GABAergic interneurons in the molecular layer or hilus. Seizure frequency significantly correlated with the loss of GABAergic interneurons in or adjacent to the granule cell layer, but not with the loss of parvalbumin-positive interneurons. These findings prioritize the loss of granule cell layer interneurons for further testing as a potential cause of temporal lobe epilepsy.

Selective Silencing of Hippocampal Parvalbumin Interneurons Induces Development of Recurrent Spontaneous Limbic Seizures in Mice.

  • Drexel M
  • J. Neurosci.
  • 2017 Aug 23

Literature context:


Abstract:

Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsies and is generally associated with malfunctioning of the hippocampal formation. Recently, a preferential loss of parvalbumin (PV) neurons has been observed in the subiculum of TLE patients and in animal models of TLE. To demonstrate a possible causative role of defunct PV neurons in the generation of TLE, we permanently inhibited GABA release selectively from PV neurons of the ventral subiculum by injecting a viral vector expressing tetanus toxin light chain in male mice. Subsequently, mice were subjected to telemetric EEG recording and video monitoring. Eighty-eight percent of the mice presented clusters of spike-wave discharges (C-SWDs; 40.0 ± 9.07/month), and 64% showed spontaneous recurrent seizures (SRSs; 5.3 ± 0.83/month). Mice injected with a control vector presented with neither C-SWDs nor SRSs. No neurodegeneration was observed due to vector injection or SRS. Interestingly, mice that presented with only C-SWDs but no SRSs, developed SRSs upon injection of a subconvulsive dose of pentylenetetrazole after 6 weeks. The initial frequency of SRSs declined by ∼30% after 5 weeks. In contrast to permanent silencing of PV neurons, transient inhibition of GABA release from PV neurons through the designer receptor hM4Di selectively expressed in PV-containing neurons transiently reduced the seizure threshold of the mice but induced neither acute nor recurrent seizures. Our data demonstrate a critical role for perisomatic inhibition mediated by PV-containing interneurons, suggesting that their sustained silencing could be causally involved in the development of TLE.SIGNIFICANCE STATEMENT Development of temporal lobe epilepsy (TLE) generally takes years after an initial insult during which maladaptation of hippocampal circuitries takes place. In human TLE and in animal models of TLE, parvalbumin neurons are selectively lost in the subiculum, the major output area of the hippocampus. The present experiments demonstrate that specific and sustained inhibition of GABA release from parvalbumin-expressing interneurons (mostly basket cells) in sector CA1/subiculum is sufficient to induce hyperexcitability and spontaneous recurrent seizures in mice. As in patients with nonlesional TLE, these mice developed epilepsy without signs of neurodegeneration. The experiments highlight the importance of the potent inhibitory action mediated by parvalbumin cells in the hippocampus and identify a potential mechanism in the development of TLE.

Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican.

  • Favuzzi E
  • Neuron
  • 2017 Aug 2

Literature context:


Abstract:

Activity-dependent neuronal plasticity is a fundamental mechanism through which the nervous system adapts to sensory experience. Several lines of evidence suggest that parvalbumin (PV+) interneurons are essential in this process, but the molecular mechanisms underlying the influence of experience on interneuron plasticity remain poorly understood. Perineuronal nets (PNNs) enwrapping PV+ cells are long-standing candidates for playing such a role, yet their precise contribution has remained elusive. We show that the PNN protein Brevican is a critical regulator of interneuron plasticity. We find that Brevican simultaneously controls cellular and synaptic forms of plasticity in PV+ cells by regulating the localization of potassium channels and AMPA receptors, respectively. By modulating Brevican levels, experience introduces precise molecular and cellular modifications in PV+ cells that are required for learning and memory. These findings uncover a molecular program through which a PNN protein facilitates appropriate behavioral responses to experience by dynamically gating PV+ interneuron function.

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

  • Soares D
  • J. Comp. Neurol.
  • 2017 Jun 15

Literature context:


Abstract:

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons.

Organization of the connections between claustrum and cortex in the mouse.

  • Wang Q
  • J. Comp. Neurol.
  • 2017 Apr 15

Literature context:


Abstract:

The connections between the claustrum and the cortex in mouse are systematically investigated with adeno-associated virus (AAV), an anterograde viral tracer. We first define the boundary and the three-dimensional structure of the claustrum based on a variety of molecular and anatomical data. From AAV injections into 42 neocortical and allocortical areas, we conclude that most cortical areas send bilateral projections to the claustrum, the majority being denser on the ipsilateral side. This includes prelimbic, infralimbic, medial, ventrolateral and lateral orbital, ventral retrosplenial, dorsal and posterior agranular insular, visceral, temporal association, dorsal and ventral auditory, ectorhinal, perirhinal, lateral entorhinal, and anteromedial, posteromedial, lateroposterior, laterointermediate, and postrhinal visual areas. In contrast, the cingulate and the secondary motor areas send denser projections to the contralateral claustrum than to the ipsilateral one. The gustatory, primary auditory, primary visual, rostrolateral visual, and medial entorhinal cortices send projections only to the ipsilateral claustrum. Primary motor, primary somatosensory and subicular areas barely send projections to either ipsi- or contralateral claustrum. Corticoclaustral projections are organized in a rough topographic manner, with variable projection strengths. We find that the claustrum, in turn, sends widespread projections preferentially to ipsilateral cortical areas with different projection strengths and laminar distribution patterns and to certain contralateral cortical areas. Our quantitative results show that the claustrum has strong reciprocal and bilateral connections with prefrontal and cingulate areas as well as strong reciprocal connections with the ipsilateral temporal and retrohippocampal areas, suggesting that it may play a crucial role in a variety of cognitive processes. J. Comp. Neurol. 525:1317-1346, 2017. © 2016 Wiley Periodicals, Inc.

Cortical hierarchy governs rat claustrocortical circuit organization.

  • White MG
  • J. Comp. Neurol.
  • 2017 Apr 15

Literature context:


Abstract:

The claustrum is a telencephalic gray matter structure with various proposed functions, including sensory integration and attentional allocation. Underlying these concepts is the reciprocal connectivity of the claustrum with most, if not all, areas of the cortex. What remains to be elucidated to inform functional hypotheses further is whether a pattern exists in the strength of connectivity between a given cortical area and the claustrum. To this end, we performed a series of retrograde neuronal tract tracer injections into rat cortical areas along the cortical processing hierarchy, from primary sensory and motor to frontal cortices. We observed that the number of claustrocortical projections increased as a function of processing hierarchy; claustrum neurons projecting to primary sensory cortices were scant and restricted in distribution across the claustrum, whereas neurons projecting to the cingulate cortex were densely packed and more evenly distributed throughout the claustrum. This connectivity pattern suggests that the claustrum may preferentially subserve executive functions orchestrated by the cingulate cortex. J. Comp. Neurol. 525:1347-1362, 2017. © 2016 Wiley Periodicals, Inc.

Funding information:
  • NIA NIH HHS - P01 AG009975(United States)

Late postnatal shifts of parvalbumin and nitric oxide synthase expression within the GABAergic and glutamatergic phenotypes of inferior colliculus neurons.

  • Fujimoto H
  • J. Comp. Neurol.
  • 2017 Mar 1

Literature context:


Abstract:

The inferior colliculus (IC) is partitioned into three subdivisions: the dorsal and lateral cortices (DC and LC) and the central nucleus (ICC), and serves as an integration center of auditory information. Recent studies indicate that a certain population of IC neurons may represent the non-GABAergic phenotype, while they express well-established cortical/hippocampal GABAergic neuron markers. In this study we used the optical disector to investigate the phenotype of IC neurons expressing parvalbumin (PV) and/or nitric oxide synthase (NOS) in C57BL/6J mice during the late postnatal period. Four major types of IC neurons were defined by the presence (+) or absence (-) of PV, NOS, and glutamic acid decarboxylase 67 (GAD67): PV+ /NOS- /GAD67+ , PV+ /NOS+ /GAD67+ , PV+ /NOS- /GAD67- , and PV- /NOS+ /GAD67- . Fluorescent in situ hybridization for vesicular glutamate transporter 2 mRNA indicated that almost all GAD67- IC neurons represented the glutamatergic phenotype. The numerical densities (NDs) of total GAD67+ IC neurons remained unchanged in all subdivisions. The NDs of PV+ /NOS- /GAD67+ neurons and PV- /NOS+ /GAD67- neurons were reduced with age in the ICC, while they remained unchanged in the DC and LC. By contrast, the NDs of PV+ /NOS+ /GAD67+ neurons and PV+ /NOS- /GAD67- neurons were increased with age in the ICC, although there were no changes in the DC and LC. The cell body size of GAD67+ IC neurons did not vary according to the expression of PV with or without NOS. The present findings indicate that the expression of PV and NOS may shift with age within the GABAergic and glutamatergic phenotypes of IC neurons during the late postnatal period. J. Comp. Neurol. 525:868-884, 2017. © 2016 Wiley Periodicals, Inc.

Funding information:
  • European Research Council - MC_UU_12022/6(International)

A Neural Circuit for Auditory Dominance over Visual Perception.

  • Song YH
  • Neuron
  • 2017 Feb 22

Literature context:


Abstract:

When conflicts occur during integration of visual and auditory information, one modality often dominates the other, but the underlying neural circuit mechanism remains unclear. Using auditory-visual discrimination tasks for head-fixed mice, we found that audition dominates vision in a process mediated by interaction between inputs from the primary visual (VC) and auditory (AC) cortices in the posterior parietal cortex (PTLp). Co-activation of the VC and AC suppresses VC-induced PTLp responses, leaving AC-induced responses. Furthermore, parvalbumin-positive (PV+) interneurons in the PTLp mainly receive AC inputs, and muscimol inactivation of the PTLp or optogenetic inhibition of its PV+ neurons abolishes auditory dominance in the resolution of cross-modal sensory conflicts without affecting either sensory perception. Conversely, optogenetic activation of PV+ neurons in the PTLp enhances the auditory dominance. Thus, our results demonstrate that AC input-specific feedforward inhibition of VC inputs in the PTLp is responsible for the auditory dominance during cross-modal integration.

The Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn.

  • Abraira VE
  • Cell
  • 2017 Jan 12

Literature context:


Abstract:

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception.

Funding information:
  • NCRR NIH HHS - S10 RR028832()
  • NIDA NIH HHS - P30 DA035756()
  • NIDA NIH HHS - R01 DA034022()
  • NIDA NIH HHS - R21 DA023643()
  • NIDCR NIH HHS - R01 DE022750()
  • NINDS NIH HHS - F32 NS077836()
  • NINDS NIH HHS - P01 NS079419()
  • NINDS NIH HHS - P30 NS072030()
  • NINDS NIH HHS - R35 NS097344()
  • NINDS NIH HHS - T32 NS007292()

Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain.

  • Martin DA
  • EBioMedicine
  • 2016 Sep 21

Literature context:


Abstract:

There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT2A-expressing excitatory neurons is directly activated by psychedelics and subsequently recruits other select cell types including subpopulations of inhibitory somatostatin and parvalbumin GABAergic interneurons, as well as astrocytes, to produce distinct and regional responses. To gather data regarding the response of specific neuronal populations, we developed methodology for fluorescence-activated cell sorting (FACS) to segregate and enrich specific cellular subtypes in the brain. These methods allow for robust neuronal sorting based on cytoplasmic epitopes followed by downstream nucleic acid analysis, expanding the utility of FACS in neuroscience research.

Funding information:
  • NIH HHS - P40 OD010440(United States)
  • NINDS NIH HHS - NS072030(United States)

Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus.

  • Byun H
  • J. Comp. Neurol.
  • 2016 Aug 1

Literature context:


Abstract:

The superior colliculus (SC) is a midbrain center involved in controlling head and eye movements in response to inputs from multiple sensory modalities. Visual inputs arise from both the retina and visual cortex and converge onto the superficial layer of the SC (sSC). Neurons in the sSC send information to deeper layers of the SC and to thalamic nuclei that modulate visually guided behaviors. Presently, our understanding of sSC neurons is impeded by a lack of molecular markers that define specific cell types. To better understand the identity and organization of sSC neurons, we took a systematic approach to investigate gene expression within four molecular families: transcription factors, cell adhesion molecules, neuropeptides, and calcium binding proteins. Our analysis revealed 12 molecules with distinct expression patterns in mouse sSC: cadherin 7, contactin 3, netrin G2, cadherin 6, protocadherin 20, retinoid-related orphan receptor β, brain-specific homeobox/POU domain protein 3b, Ets variant gene 1, substance P, somatostatin, vasoactive intestinal polypeptide, and parvalbumin. Double labeling experiments, by either in situ hybridization or immunostaining, demonstrated that the 12 molecular markers collectively define 10 different sSC neuronal types. The characteristic positions of these cell types divide the sSC into four distinct layers. The 12 markers identified here will serve as valuable tools to examine molecular mechanisms that regulate development of sSC neuronal types. These markers could also be used to examine the connections between specific cell types that form retinocollicular, corticocollicular, or colliculothalamic pathways. J. Comp. Neurol. 524:2300-2321, 2016. © 2016 Wiley Periodicals, Inc.

Funding information:
  • NINDS NIH HHS - R01 NS073857(United States)

The temporal profile of retinal cell genesis in the marmoset monkey.

  • Hendrickson A
  • J. Comp. Neurol.
  • 2016 Apr 15

Literature context:


Abstract:

The New World marmoset monkey (Callithrix jacchus) has a relatively short gestational period compared with other primates but possesses a retina at a similar stage of maturation by birth. Previous studies have highlighted that the complex fovea of the marmoset undergoes a more rapid postnatal development in comparison with the Macaca monkey, reaching a mature stage earlier than these species. In this current study, we examined the prenatal proliferation profile of cells in the entire retina employing the thymidine analogs and also determined their phenotype by double-label immunocytochemistry using type-specific markers. Akin to other primate species, we demonstrate a centroperipheral gradient in the emergence of both neurons and Müller glia with cones, ganglion cells, and horizontal cells generated first in the fovea at fetal day (Fd)70-74 and with the last generated at the retinal edge at Fd115. Rods, bipolar cells, amacrine cells, displaced amacrine cells, and Müller glia were generated between Fd76 and Fd135 along the same gradient. Similar to foveal development, marmoset neuronal generation was rapid, only taking 51% of gestation whereas in Macaca this takes 81%.

Funding information:
  • NICHD NIH HHS - HD058056(United States)

Ketamine Administration During the Second Postnatal Week Alters Synaptic Properties of Fast-Spiking Interneurons in the Medial Prefrontal Cortex of Adult Mice.

  • Jeevakumar V
  • Cereb. Cortex
  • 2016 Mar 3

Literature context:


Abstract:

The N-methyl-D-aspartic acid (NMDA)-hypofunction theory of schizophrenia suggests that schizophrenia is associated with a loss of NMDA receptors, specifically on corticolimbic parvalbumin (PV)-expressing GABAergic interneurons, leading to disinhibition of pyramidal cells and cortical desynchronization. However, the presumed changes in glutamatergic inputs onto PV interneurons have not been tested directly. We treated mice with the NMDAR antagonist ketamine during the second postnatal week and investigated persistent cellular changes in the adult medial prefrontal cortex (mPFC) using whole-cell patch-clamp recordings and immunohistochemistry. Parvalbumin expression in the mPFC was reduced in ketamine-treated (KET) mice, and γ-aminobutyric acid release onto pyramidal cells was reduced in layers 2/3, but not layer 5. Consistent with pyramidal cell disinhibition the frequency of spontaneous glutamatergic inputs onto PV cells was also increased in KET mice. Furthermore, developmental ketamine treatment resulted in an increased NMDA:AMPA ratio in evoked synaptic currents and larger amplitudes of spontaneous NMDAR currents, indicating a homeostatic upregulation of NMDARs in PV interneurons. This upregulation was specific to NR2B subunits, without concomitant alterations in currents through NR2A subunits. These changes altered synaptic integration at PV cells during trains of excitatory postsynaptic potentials. These changes likely impact synaptic coincidence detection and impair cortical network function in the NMDAR antagonism model of schizophrenia.

Mapping the mosaic sequence of primate visual cortical development.

  • Mundinano IC
  • Front Neuroanat
  • 2015 Nov 5

Literature context:


Abstract:

Traditional "textbook" theory suggests that the development and maturation of visual cortical areas occur as a wave from V1. However, more recent evidence would suggest that this is not the case, and the emergence of extrastriate areas occurs in a non-hierarchical fashion. This proposition comes from both physiological and anatomical studies but the actual developmental sequence of extrastriate areas remains unknown. In the current study, we examined the development and maturation of the visual cortex of the marmoset monkey, a New World simian, from embryonic day 130 (15 days prior to birth) through to adulthood. Utilizing the well-described expression characteristics of the calcium-binding proteins calbindin and parvalbumin, and nonphosphorylated neurofilament for the pyramidal neurons, we were able to accurately map the sequence of development and maturation of the visual cortex. To this end, we demonstrated that both V1 and middle temporal area (MT) emerge first and that MT likely supports dorsal stream development while V1 supports ventral stream development. Furthermore, the emergence of the dorsal stream-associated areas was significantly earlier than ventral stream areas. The difference in the temporal development of the visual streams is likely driven by a teleological requirement for specific visual behavior in early life.

Ketamine administration during the second postnatal week induces enduring schizophrenia-like behavioral symptoms and reduces parvalbumin expression in the medial prefrontal cortex of adult mice.

  • Jeevakumar V
  • Behav. Brain Res.
  • 2015 Apr 1

Literature context:


Abstract:

Dysfunctions in the GABAergic system are considered a core feature of schizophrenia. Pharmacological blockade of NMDA receptors (NMDAR), or their genetic ablation in parvalbumin (PV)-expressing GABAergic interneurons can induce schizophrenia-like behavior in animals. NMDAR-mediated currents shape the maturation of GABAergic interneurons during a critical period of development, making transient blockade of NMDARs during this period an attractive model for the developmental changes that occur in the course of schizophrenia's pathophysiology. Here, we examined whether developmental administration of the non-competitive NMDAR antagonist ketamine results in persistent deficits in PFC-dependent behaviors in adult animals. Mice received injections of ketamine (30mg/kg) on postnatal days (PND) 7, 9 and 11, and then tested on a battery of behavioral experiments aimed to mimic major symptoms of schizophrenia in adulthood (between PND 90 and 120). Ketamine treatment reduced the number of cells that expressed PV in the PFC by ∼60% as previously described. Ketamine affected performance in an attentional set-shifting task, impairing the ability of the animals to perform an extradimensional shift to acquire a new strategy. Ketamine-treated animals showed deficits in latent inhibition, novel-object recognition and social novelty detection compared to their SAL-treated littermates. These deficits were not a result of generalized anxiety, as both groups performed comparably on an elevated plus maze. Ketamine treatment did not cause changes in amphetamine-induced hyperlocomotion that are often taken as measures for the positive-like symptoms of the disorder. Thus, ketamine administration during development appears to be a useful model for inducing cognitive and negative symptoms of schizophrenia.

Funding information:
  • NCRR NIH HHS - P20 RR16462(United States)

Subclass-specific formation of perineuronal nets around parvalbumin-expressing GABAergic neurons in Ammon's horn of the mouse hippocampus.

  • Yamada J
  • J. Comp. Neurol.
  • 2015 Apr 1

Literature context:


Abstract:

Perineuronal nets (PNNs) are closely associated with parvalbumin-positive (PV+) neurons, and play a major role in controlling developmental neural plasticity. Considering the recent advances in classification of PV+ neurons, here we aimed to clarify whether PNNs might be associated with specific subclasses of PV+ neurons in the hippocampus. In this study, we labeled PNNs by Wisteria floribunda agglutinin (WFA), and classified PV+ neurons based on the combination of cellular location, molecular expression (neuropeptide Y [NPY], somatostatin [SOM], special AT-rich sequence-binding protein-1 [SATB1]), and retrograde tracing through stereotaxic injection of Fluoro-Gold (FG) into the medial septum. The criteria of each subclass can be summarized as follows: axo-axonic cells, PV+/SATB1-/NPY- cells in the stratum pyramidale; basket cells, PV+/SATB1+/NPY- cells in the stratum pyramidale; bistratified cells, PV+/SATB1+/NPY+ cells in the stratum pyramidale; oriens-lacunosum-moleculare (O-LM) cells, PV+/SOM+/FG- cells in the stratum oriens; hippocampo-septal projection (H-S) cells, and PV+/SOM+/FG+ cells in the stratum oriens. The ratios of formation of WFA+ PNNs around each subclass of PV+ neurons were estimated according to the optical disector principle. The vast majority (over 90%) of putative PV+ basket cells were surrounded by PNNs, while only a minor population (less than 10%) of putative PV+ axo-axonic, O-LM, and H-S cells were enwrapped with PNNs. The ratios of formation of PNNs around putative PV+ bistratified cells were intermediate (25-50%). These findings indicate that PNNs may be specifically associated with PV+ basket cells, and also provide a key to understand the functional significance of PNNs and PV+ neurons in the hippocampus.

Analysis of bipolar and amacrine populations in marmoset retina.

  • Weltzien F
  • J. Comp. Neurol.
  • 2015 Feb 1

Literature context:


Abstract:

About 15 parallel ganglion cell pathways transmit visual signals to the brain, but the interneuron (bipolar and amacrine) populations providing input to ganglion cells remain poorly understood in primate retina. We carried out a quantitative analysis of the inner nuclear layer in the retina of the marmoset (Callithrix jacchus). Vertical Vibratome sections along the horizontal meridian were processed with immunohistochemical markers. Image stacks were taken with a confocal microscope, and densities of cell populations were determined. The density of flat midget bipolar cells fell from 15,746 cells/mm(2) at 1 mm (8 deg) to 7,827 cells/mm(2) at 3 mm (25 deg). The rod bipolar cell density fell from 8,640 cells/mm(2) at 1 mm to 4,278 cells/mm(2) at 3 mm, but the ratio of the two bipolar cell types did not change with eccentricity. The amacrine cell density ranged from 30,000 cells/mm(2) at 8 deg to less than 15,000 cells/mm(2) at 25 deg, but throughout the retina, the ratio of glycinergic to γ-aminobutyric acid (GABA)ergic to amacrine cells remained relatively constant. The fractions of rod bipolar, cone bipolar, amacrine, Müller, and horizontal cells of all cells in the inner nuclear layer were comparable in central and peripheral retina. Marmosets had lower proportions of midget bipolar and rod bipolar in comparison with macaque. These differences were correlated with differences in rod and cone densities between the two species and did not reflect fundamental differences in the wiring between the two species.

Loss of cyclin-dependent kinase 5 from parvalbumin interneurons leads to hyperinhibition, decreased anxiety, and memory impairment.

  • Rudenko A
  • J. Neurosci.
  • 2015 Feb 11

Literature context:


Abstract:

Perturbations in fast-spiking parvalbumin (PV) interneurons are hypothesized to be a major component of various neuropsychiatric disorders; however, the mechanisms regulating PV interneurons remain mostly unknown. Recently, cyclin-dependent kinase 5 (Cdk5) has been shown to function as a major regulator of synaptic plasticity. Here, we demonstrate that genetic ablation of Cdk5 in PV interneurons in mouse brain leads to an increase in GABAergic neurotransmission and impaired synaptic plasticity. PVCre;fCdk5 mice display a range of behavioral abnormalities, including decreased anxiety and memory impairment. Our results reveal a central role of Cdk5 expressed in PV interneurons in gating inhibitory neurotransmission and underscore the importance of such regulation during behavioral tasks. Our findings suggest that Cdk5 can be considered a promising therapeutic target in a variety of conditions attributed to inhibitory interneuronal dysfunction, such as epilepsy, anxiety disorders, and schizophrenia.

Parallel prefrontal pathways reach distinct excitatory and inhibitory systems in memory-related rhinal cortices.

  • Bunce JG
  • J. Comp. Neurol.
  • 2013 Dec 15

Literature context:


Abstract:

To investigate how prefrontal cortices impinge on medial temporal cortices we labeled pathways from the anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) in rhesus monkeys to compare their relationship with excitatory and inhibitory systems in rhinal cortices. The ACC pathway terminated mostly in areas 28 and 35 with a high proportion of large terminals, whereas the pOFC pathway terminated mostly through small terminals in area 36 and sparsely in areas 28 and 35. Both pathways terminated in all layers. Simultaneous labeling of pathways and distinct neurochemical classes of inhibitory neurons, followed by analyses of appositions of presynaptic and postsynaptic fluorescent signal, or synapses, showed overall predominant association with spines of putative excitatory neurons, but also significant interactions with presumed inhibitory neurons labeled for calretinin, calbindin, or parvalbumin. In the upper layers of areas 28 and 35 the ACC pathway was associated with dendrites of neurons labeled with calretinin, which are thought to disinhibit neighboring excitatory neurons, suggesting facilitated hippocampal access. In contrast, in area 36 pOFC axons were associated with dendrites of calbindin neurons, which are poised to reduce noise and enhance signal. In the deep layers, both pathways innervated mostly dendrites of parvalbumin neurons, which strongly inhibit neighboring excitatory neurons, suggesting gating of hippocampal output to other cortices. These findings suggest that the ACC, associated with attention and context, and the pOFC, associated with emotional valuation, have distinct contributions to memory in rhinal cortices, in processes that are disrupted in psychiatric diseases.

Funding information:
  • Intramural NIH HHS - (United States)

Nuclear receptor COUP-TFII-expressing neocortical interneurons are derived from the medial and lateral/caudal ganglionic eminence and define specific subsets of mature interneurons.

  • Cai Y
  • J. Comp. Neurol.
  • 2013 Feb 1

Literature context:


Abstract:

Neocortical GABAergic interneurons in rodents originate from subpallial progenitor zones. The majority of mouse neocortical interneurons are derived from the medial and caudal ganglionic eminences (MGE and CGE, respectively) and the preoptic area (POA). It is controversial whether the lateral ganglionic eminence (LGE) also generates neocortical interneurons. Previously it was shown that the transcription factor COUP-TFII is expressed in the CGE; here we show that COUP-TFII is also expressed in the dorsal MGE, dorsal LGE (dMGE and dLGE, respectively), and POA. In the adult neocortex, COUP-TFII+/somatostatin (SOM)+ interneurons are mainly located in layer V. Using a genetic fate-mapping approach (Shh-Cre and Nkx2.1-Cre), we demonstrate that the POA and ventral MGE do not give rise to COUP-TFII+ neocortical interneurons, suggesting that the dMGE is the source of COUP-TFII+/SOM+ neocortical interneurons. We also observed a migratory stream of COUP-TFII+/Sp8+ cells emanating from the dLGE and CGE to the neocortex mainly through the subventricular zone at later embryonic stages. Slice culture experiments in which dLGE progenitors were labeled with BrdU provided additional evidence that the dLGE generates neocortical interneurons. While earlier-born dMGE-derived COUP-TFII+ interneurons occupy cortical layer V, later-born dLGE- and CGE-derived COUP-TFII+ ones preferentially occupy superficial cortical layers. A similar laminar distribution was observed following neonatal transplantation of embryonic day (E)14.5 dMGE and E15.5 dLGE. These results provide novel information about interneuron fate and position from spatially and temporally distinct origins in the ganglionic eminences.

Funding information:
  • Howard Hughes Medical Institute - R01 GM060124(United States)
  • NINDS NIH HHS - 5R01NS037070(United States)