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Streptavidin, Alexa Fluor 488 conjugate antibody

RRID:AB_2315383

Antibody ID

AB_2315383

Target Antigen

Proper Citation

(Molecular Probes Cat# S32354, RRID:AB_2315383)

Clonality

unknown

Comments

Discontinued; This product offered by Molecular Probes (Invitrogen), now part of Thermo Fisher

Vendor

Molecular Probes

Cat Num

S32354 also S32354

The cellular prion protein promotes olfactory sensory neuron survival and axon targeting during adult neurogenesis.

  • Parrie LE
  • Dev. Biol.
  • 2018 Jun 1

Literature context:


Abstract:

The cellular prion protein (PrPC) has been associated with diverse biological processes including cell signaling, neurogenesis, and neuroprotection, but its physiological function(s) remain ambiguous. Here we determine the role of PrPC in adult neurogenesis using the olfactory system model in transgenic mice. Olfactory sensory neurons (OSNs) within the olfactory sensory epithelium (OSE) undergo neurogenesis, integration, and turnover even into adulthood. The neurogenic processes of proliferation, differentiation/maturation, and axon targeting were evaluated in wild type, PrP-overexpressing, and PrP-null transgenic mice. Our results indicate that PrPC plays a role in maintaining mature OSNs within the epithelium: overexpression of PrPC resulted in greater survival of mitotically active cells within the OSE, whereas absence of prion protein resulted in fewer cells being maintained over time. These results are supported by both quantitative PCR analysis of gene expression and protein analysis characteristic of OSN differentiation. Finally, evaluation of axon migration determined that OSN axon targeting in the olfactory bulb is PrPC dose-dependent. Together, these findings provide new mechanistic insight into the neuroprotective role for PrPC in adult OSE neurogenesis, whereby more mature neurons are stably maintained in animals expressing PrPC.

Funding information:
  • NIAID NIH HHS - AI81789(United States)
  • NINDS NIH HHS - R21 NS096662(United States)

Evidence for neurogenesis in the medial cortex of the leopard gecko, Eublepharis macularius.

  • McDonald RP
  • Sci Rep
  • 2018 Jun 25

Literature context:


Abstract:

Although lizards are often described as having robust neurogenic abilities, only a handful of the more than 6300 species have been explored. Here, we provide the first evidence of homeostatic neurogenesis in the leopard gecko (Eublepharis macularius). We focused our study on the medial cortex, homologue of the mammalian hippocampal formation. Using immunostaining, we identified proliferating pools of neural stem/progenitor cells within the sulcus septomedialis, the pseudostratified ventricular zone adjacent to the medial cortex. Consistent with their identification as radial glia, these cells expressed SOX2, glial fibrillary acidic protein, and Vimentin, and demonstrated a radial morphology. Using a 5-bromo-2'-deoxyuridine cell tracking strategy, we determined that neuroblast migration from the ventricular zone to the medial cortex takes ~30-days, and that newly generated neuronal cells survived for at least 140-days. We also found that cell proliferation within the medial cortex was not significantly altered following rupture of the tail spinal cord (as a result of the naturally evolved process of caudal autotomy). We conclude that the sulcus septomedialis of the leopard gecko demonstrates all the hallmarks of a neurogenic niche.

Funding information:
  • Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturell - 400358()
  • NCI NIH HHS - R01 CA97063(United States)

Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2.

  • Mendez-Bermudez A
  • Mol. Cell
  • 2018 May 3

Literature context:


Abstract:

Hard-to-replicate regions of chromosomes (e.g., pericentromeres, centromeres, and telomeres) impede replication fork progression, eventually leading, in the event of replication stress, to chromosome fragility, aging, and cancer. Our knowledge of the mechanisms controlling the stability of these regions is essentially limited to telomeres, where fragility is counteracted by the shelterin proteins. Here we show that the shelterin subunit TRF2 ensures progression of the replication fork through pericentromeric heterochromatin, but not centromeric chromatin. In a process involving its N-terminal basic domain, TRF2 binds to pericentromeric Satellite III sequences during S phase, allowing the recruitment of the G-quadruplex-resolving helicase RTEL1 to facilitate fork progression. We also show that TRF2 is required for the stability of other heterochromatic regions localized throughout the genome, paving the way for future research on heterochromatic replication and its relationship with aging and cancer.

Funding information:
  • Medical Research Council - (United Kingdom)

An Optical Neuron-Astrocyte Proximity Assay at Synaptic Distance Scales.

  • Octeau JC
  • Neuron
  • 2018 Apr 4

Literature context:


Abstract:

Astrocytes are complex bushy cells that serve important functions through close contacts between their processes and synapses. However, the spatial interactions and dynamics of astrocyte processes relative to synapses have proven problematic to study in adult living brain tissue. Here, we report a genetically targeted neuron-astrocyte proximity assay (NAPA) to measure astrocyte-synapse spatial interactions within intact brain preparations and at synaptic distance scales. The method exploits resonance energy transfer between extracellularly displayed fluorescent proteins targeted to synapses and astrocyte processes. We validated the method in the striatal microcircuitry following in vivo expression. We determined the proximity of striatal astrocyte processes to distinct neuronal input pathways, to D1 and D2 medium spiny neuron synapses, and we evaluated how astrocyte-to-excitatory synapse proximity changed following cortical afferent stimulation, during ischemia and in a model of Huntington's disease. NAPA provides a simple approach to measure astrocyte-synapse spatial interactions in a variety of experimental scenarios. VIDEO ABSTRACT.

Funding information:
  • NCI NIH HHS - R01 CA104926(United States)

Rapid nonapeptide synthesis during a critical period of development in the prairie vole: plasticity of the paraventricular nucleus of the hypothalamus.

  • Kelly AM
  • Brain Struct Funct
  • 2018 Mar 11

Literature context:


Abstract:

Vasopressin (VP) and oxytocin (OT) are involved in modulating basic physiology and numerous social behaviors. Although the anatomical distributions of nonapeptide neurons throughout development have been described, the functional roles of VP and OT neurons during development are surprisingly understudied, and it is unknown whether they exhibit functional changes throughout early development. We utilized an acute social isolation paradigm to determine if VP and OT neural responses in eight nonapeptide cell groups differ at three different stages of early development in prairie voles. We tested pups at ages that are representative of the three rapid growth stages of the developing brain: postnatal day (PND)2 (closed eyes; poor locomotion), PND9 (eye opening; locomotion; peak brain growth spurt), and PND21 (weaning). Neural responses were examined in pups that (1) were under normal family conditions with their parents and siblings, (2) were isolated from their parents and siblings and then reunited, and (3) were isolated from their parents and siblings. We found that VP and OT neural activity (as assessed via Fos co-localization) did not differ in response to social condition across development. However, remarkably rapid VP and OT synthesis in response to social isolation was observed only in the paraventricular nucleus of the hypothalamus (PVN) and only in PND9 pups. These results suggest that PVN nonapeptide neurons exhibit distinct cellular properties during a critical period of development, allowing nonapeptide neurons to rapidly upregulate peptide production in response to stressors on a much shorter timescale than has been observed in adult animals.

Funding information:
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development - HD079573()
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development - HD081959()
  • NIGMS NIH HHS - GM99722(United States)

High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies.

  • Youn JY
  • Mol. Cell
  • 2018 Feb 1

Literature context:


Abstract:

mRNA processing, transport, translation, and ultimately degradation involve a series of dedicated protein complexes that often assemble into large membraneless structures such as stress granules (SGs) and processing bodies (PBs). Here, systematic in vivo proximity-dependent biotinylation (BioID) analysis of 119 human proteins associated with different aspects of mRNA biology uncovers 7424 unique proximity interactions with 1,792 proteins. Classical bait-prey analysis reveals connections of hundreds of proteins to distinct mRNA-associated processes or complexes, including the splicing and transcriptional elongation machineries (protein phosphatase 4) and the CCR4-NOT deadenylase complex (CEP85, RNF219, and KIAA0355). Analysis of correlated patterns between endogenous preys uncovers the spatial organization of RNA regulatory structures and enables the definition of 144 core components of SGs and PBs. We report preexisting contacts between most core SG proteins under normal growth conditions and demonstrate that several core SG proteins (UBAP2L, CSDE1, and PRRC2C) are critical for the formation of microscopically visible SGs.

Funding information:
  • NIDDK NIH HHS - DK071041(United States)

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)

Neuronal activity determines distinct gliotransmitter release from a single astrocyte.

  • Covelo A
  • Elife
  • 2018 Jan 30

Literature context:


Abstract:

Accumulating evidence indicates that astrocytes are actively involved in brain function by regulating synaptic activity and plasticity. Different gliotransmitters, such as glutamate, ATP, GABA or D-serine, released form astrocytes have been shown to induce different forms of synaptic regulation. However, whether a single astrocyte may release different gliotransmitters is unknown. Here we show that mouse hippocampal astrocytes activated by endogenous (neuron-released endocannabinoids or GABA) or exogenous (single astrocyte Ca2+ uncaging) stimuli modulate putative single CA3-CA1 hippocampal synapses. The astrocyte-mediated synaptic modulation was biphasic and consisted of an initial glutamate-mediated potentiation followed by a purinergic-mediated depression of neurotransmitter release. The temporal dynamic properties of this biphasic synaptic regulation depended on the firing frequency and duration of the neuronal activity that stimulated astrocytes. Present results indicate that single astrocytes can decode neuronal activity and, in response, release distinct gliotransmitters to differentially regulate neurotransmission at putative single synapses.

Funding information:
  • Human Frontier Science Program - RGP0036/2014()
  • NIAID NIH HHS - R01 AI107966(United States)
  • NINDS NIH HHS - R01 NS097312()
  • NINDS NIH HHS - R01NS097312-01()

PTEN deletion increases hippocampal granule cell excitability in male and female mice.

  • Santos VR
  • Neurobiol. Dis.
  • 2017 Dec 31

Literature context:


Abstract:

Deletion of the mTOR pathway inhibitor PTEN from postnatally-generated hippocampal dentate granule cells causes epilepsy. Here, we conducted field potential, whole cell recording and single cell morphology studies to begin to elucidate the mechanisms by which granule cell-specific PTEN-loss produces disease. Cells from both male and female mice were recorded to identify sex-specific effects. PTEN knockout granule cells showed altered intrinsic excitability, evident as a tendency to fire in bursts. PTEN knockout granule cells also exhibited increased frequency of spontaneous excitatory synaptic currents (sEPSCs) and decreased frequency of inhibitory currents (sIPSCs), further indicative of a shift towards hyperexcitability. Morphological studies of PTEN knockout granule cells revealed larger dendritic trees, more dendritic branches and an impairment of dendrite self-avoidance. Finally, cells from both female control and female knockout mice received more sEPSCs and more sIPSCs than corresponding male cells. Despite the difference, the net effect produced statistically equivalent EPSC/IPSC ratios. Consistent with this latter observation, extracellularly evoked responses in hippocampal slices were similar between male and female knockouts. Both groups of knockouts were abnormal relative to controls. Together, these studies reveal a host of physiological and morphological changes among PTEN knockout cells likely to underlie epileptogenic activity. SIGNIFICANCE STATEMENT: Hyperactivation of the mTOR pathway is associated with numerous neurological diseases, including autism and epilepsy. Here, we demonstrate that deletion of the mTOR negative regulator, PTEN, from a subset of hippocampal dentate granule impairs dendritic patterning, increases excitatory input and decreases inhibitory input. We further demonstrate that while granule cells from female mice receive more excitatory and inhibitory input than males, PTEN deletion produces mostly similar changes in both sexes. Together, these studies provide new insights into how the relatively small number (≈200,000) of PTEN knockout granule cells instigates the development of the profound epilepsy syndrome evident in both male and female animals in this model.

Synapse-specific astrocyte gating of amygdala-related behavior.

  • Martin-Fernandez M
  • Nat. Neurosci.
  • 2017 Nov 2

Literature context:


Abstract:

The amygdala plays key roles in fear and anxiety. Studies of the amygdala have largely focused on neuronal function and connectivity. Astrocytes functionally interact with neurons, but their role in the amygdala remains largely unknown. We show that astrocytes in the medial subdivision of the central amygdala (CeM) determine the synaptic and behavioral outputs of amygdala circuits. To investigate the role of astrocytes in amygdala-related behavior and identify the underlying synaptic mechanisms, we used exogenous or endogenous signaling to selectively activate CeM astrocytes. Astrocytes depressed excitatory synapses from basolateral amygdala via A1 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A2A receptor activation. Furthermore, astrocytic activation decreased the firing rate of CeM neurons and reduced fear expression in a fear-conditioning paradigm. Therefore, we conclude that astrocyte activity determines fear responses by selectively regulating specific synapses, which indicates that animal behavior results from the coordinated activity of neurons and astrocytes.

Dmrt5, a Novel Neurogenic Factor, Reciprocally Regulates Lhx2 to Control the Neuron-Glia Cell-Fate Switch in the Developing Hippocampus.

  • Muralidharan B
  • J. Neurosci.
  • 2017 Nov 15

Literature context:


Abstract:

Regulation of the neuron-glia cell-fate switch is a critical step in the development of the CNS. Previously, we demonstrated that Lhx2 is a necessary and sufficient regulator of this process in the mouse hippocampal primordium, such that Lhx2 overexpression promotes neurogenesis and suppresses gliogenesis, whereas loss of Lhx2 has the opposite effect. We tested a series of transcription factors for their ability to mimic Lhx2 overexpression and suppress baseline gliogenesis, and also to compensate for loss of Lhx2 and suppress the resulting enhanced level of gliogenesis in the hippocampus. Here, we demonstrate a novel function of Dmrt5/Dmrta2 as a neurogenic factor in the developing hippocampus. We show that Dmrt5, as well as known neurogenic factors Neurog2 and Pax6, can each not only mimic Lhx2 overexpression, but also can compensate for loss of Lhx2 to different extents. We further uncover a reciprocal regulatory relationship between Dmrt5 and Lhx2, such that each can compensate for loss of the other. Dmrt5 and Lhx2 also have opposing regulatory control on Pax6 and Neurog2, indicating a complex bidirectionally regulated network that controls the neuron-glia cell-fate switch.SIGNIFICANCE STATEMENT We identify Dmrt5 as a novel regulator of the neuron-glia cell-fate switch in the developing hippocampus. We demonstrate Dmrt5 to be neurogenic, and reciprocally regulated by Lhx2: loss of either factor promotes gliogenesis; overexpression of either factor suppresses gliogenesis and promotes neurogenesis; each can substitute for loss of the other. Furthermore, each factor has opposing effects on established neurogenic genes Neurog2 and Pax6 Dmrt5 is known to suppress their expression, and we show that Lhx2 is required to maintain it. Our study reveals a complex regulatory network with bidirectional control of a fundamental feature of CNS development, the control of the production of neurons versus astroglia in the developing hippocampus.Finally, we confirm that Lhx2 binds a highly conserved putative enhancer of Dmrt5, suggesting an evolutionarily conserved regulatory relationship between these factors. Our findings uncover a complex network that involves Lhx2, Dmrt5, Neurog2, and Pax6, and that ensures the appropriate amount and timing of neurogenesis and gliogenesis in the developing hippocampus.

Funding information:
  • Howard Hughes Medical Institute - (United States)

RING Finger Protein 38 Is a Neuronal Protein in the Brain of Nile Tilapia, Oreochromis niloticus.

  • Cham KL
  • Front Neuroanat
  • 2017 Sep 15

Literature context:


Abstract:

Really interesting new gene (RING) finger protein is a type of zinc-binding motif found in a large family of functionally distinct proteins. RING finger proteins are involved in diverse cellular processes including apoptosis, DNA repair, cell cycle, signal transduction, tumour suppressor, vesicular transport, and peroxisomal biogenesis. RING finger protein 38 (RNF38) is a member of the family whose functions remain unknown. To gain insight into the putative effects of RNF38 in the central nervous system, we localised its expression. The aim of this study was to identify the neuroanatomical location(s) of rnf38 mRNA and its peptide, determine the type of RNF38-expressing cells, and measure rnf38 gene expression in the brain of male tilapia. The distributions of rnf38 mRNA and its peptide were visualised using in situ hybridisation with digoxigenin-labelled RNA antisense and immunocytochemistry, respectively. Both were identically distributed throughout the brain, including the telencephalon, preoptic area, optic tectum, hypothalamus, cerebellum, and the hindbrain. Double-labelling immunocytochemistry for RNF38 and the neuronal marker HuC/D showed that most but not all RNF38 protein was expressed in neuronal nuclei. Quantitative real-time polymerase chain reaction showed the highest level of rnf38 mRNA in the midbrain, followed by the preoptic area, cerebellum, optic tectum, telencephalon, hindbrain and hypothalamus. These findings reveal a differential spatial pattern of RNF38 in the tilapia brain, suggesting that it has potentially diverse functions related to neuronal activity.

A comparative analysis of the physiological properties of neurons in the anterolateral bed nucleus of the stria terminalis in the Mus musculus, Rattus norvegicus, and Macaca mulatta.

  • Daniel SE
  • J. Comp. Neurol.
  • 2017 Jun 15

Literature context:


Abstract:

The anterolateral group of the bed nucleus of the stria terminalis (BNSTALG ) is a critical modulator of a variety of rodent and primate behaviors spanning anxiety behavior and drug addiction. Three distinct neuronal cell types have been previously defined in the rat BNSTALG based on differences in the voltage-response to hyperpolarizing and depolarizing current injection. Differences in genetic expression profile between these three cell types suggest electrophysiological cell type may be an indicator for functional differences in the circuit of the rat BNSTALG . Although the behavioral role of the BNST is conserved across species, it is unknown if the same electrophysiological cell types exist in the BNSTALG of the mouse and nonhuman primate. Here, we used whole-cell patch clamp electrophysiology and neuronal reconstructions of biocytin-filled neurons to compare and contrast the electrophysiological and morphological properties of neurons in the BNSTALG from the mouse, rat, and rhesus macaque. We provide evidence that the BNSTALG of all three species contains neurons that match the three defined cell types found in the rat; however, there are intriguing differences in the relative frequency of these cell types as well as electrophysiological and morphological properties of the BNSTALG neurons across species. This study suggests that the overall landscape of the BNSTALG in the primate and mouse may be similar to that of the rat in some aspects but perhaps significantly different in others.

Funding information:
  • NHLBI NIH HHS - R01 HL108678-01(United States)
  • NIH HHS - P51 OD011132()
  • NIMH NIH HHS - F31 MH097331()
  • NIMH NIH HHS - R01 MH072908()

BK Channels Mediate Synaptic Plasticity Underlying Habituation in Rats.

  • Zaman T
  • J. Neurosci.
  • 2017 Apr 26

Literature context:


Abstract:

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, using patch-clamp recordings and voltage-sensitive dye imaging in slices. Furthermore, positive modulation of BK channels in vivo can enhance short-term habituation. Although results using different approaches do not always perfectly align, together they provide convincing evidence for a crucial role of BK channel phosphorylation in synaptic depression underlying short-term habituation of startle. We also show that this mechanism can be targeted to enhance short-term habituation and therefore to potentially ameliorate sensory filtering deficits associated with psychiatric disorders.SIGNIFICANCE STATEMENT Short-term habituation is the most fundamental form of implicit learning. Habituation also represents a filter for inundating sensory information, which is disrupted in autism, schizophrenia, and other psychiatric disorders. Habituation has been studied in different organisms and behavioral models and is thought to be caused by synaptic depression in respective pathways. The underlying molecular mechanisms, however, are poorly understood. We here identify, for the first time, a BK channel-dependent molecular synaptic mechanism leading to synaptic depression that is crucial for habituation, and we discuss the significance of our findings for potential treatments enhancing habituation.

Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks.

  • Perea G
  • Elife
  • 2016 Dec 24

Literature context:


Abstract:

Interneurons are critical for proper neural network function and can activate Ca2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.

Funding information:
  • NIMH NIH HHS - P50 MH100024()
  • NINDS NIH HHS - R01 NS097312()

Cerebellar Premotor Output Neurons Collateralize to Innervate the Cerebellar Cortex.

  • Houck BD
  • J. Comp. Neurol.
  • 2015 Oct 15

Literature context:


Abstract:

Motor commands computed by the cerebellum are hypothesized to use corollary discharge, or copies of outgoing commands, to accelerate motor corrections. Identifying sources of corollary discharge, therefore, is critical for testing this hypothesis. Here we verified that the pathway from the cerebellar nuclei to the cerebellar cortex in mice includes collaterals of cerebellar premotor output neurons, mapped this collateral pathway, and identified its postsynaptic targets. Following bidirectional tracer injections into a distal target of the cerebellar nuclei, the ventrolateral thalamus, we observed retrogradely labeled somata in the cerebellar nuclei and mossy fiber terminals in the cerebellar granule layer, consistent with collateral branching. Corroborating these observations, bidirectional tracer injections into the cerebellar cortex retrogradely labeled somata in the cerebellar nuclei and boutons in the ventrolateral thalamus. To test whether nuclear output neurons projecting to the red nucleus also collateralize to the cerebellar cortex, we used a Cre-dependent viral approach, avoiding potential confounds of direct red nucleus-to-cerebellum projections. Injections of a Cre-dependent GFP-expressing virus into Ntsr1-Cre mice, which express Cre selectively in the cerebellar nuclei, retrogradely labeled somata in the interposed nucleus, and putative collateral branches terminating as mossy fibers in the cerebellar cortex. Postsynaptic targets of all labeled mossy fiber terminals were identified using immunohistochemical Golgi cell markers and electron microscopic profiles of granule cells, indicating that the collaterals of nuclear output neurons contact both Golgi and granule cells. These results clarify the organization of a subset of nucleocortical projections that constitute an experimentally accessible corollary discharge pathway within the cerebellum.

GABAergic projections from the medial septum selectively inhibit interneurons in the medial entorhinal cortex.

  • Gonzalez-Sulser A
  • J. Neurosci.
  • 2014 Dec 10

Literature context:


Abstract:

The medial septum (MS) is required for theta rhythmic oscillations and grid cell firing in the medial entorhinal cortex (MEC). While GABAergic, glutamatergic, and cholinergic neurons project from the MS to the MEC, their synaptic targets are unknown. To investigate whether MS neurons innervate specific layers and cell types in the MEC, we expressed channelrhodopsin-2 in mouse MS neurons and used patch-clamp recording in brain slices to determine the response to light activation of identified cells in the MEC. Following activation of MS axons, we observed fast monosynaptic GABAergic IPSPs in the majority (>60%) of fast-spiking (FS) and low-threshold-spiking (LTS) interneurons in all layers of the MEC, but in only 1.5% of nonstellate principal cells (NSPCs) and in no stellate cells. We also observed fast glutamatergic responses to MS activation in a minority (<5%) of NSPCs, FS, and LTS interneurons. During stimulation of MS inputs at theta frequency (10 Hz), the amplitude of GABAergic IPSPs was maintained, and spike output from LTS and FS interneurons was entrained at low (25-60 Hz) and high (60-180 Hz) gamma frequencies, respectively. By demonstrating cell type-specific targeting of the GABAergic projection from the MS to the MEC, our results support the idea that the MS controls theta frequency activity in the MEC through coordination of inhibitory circuits.

Funding information:
  • NIDCD NIH HHS - R01 DC001856(United States)

Expression of GABAergic and glutamatergic phenotypic markers in hypothalamic proopiomelanocortin neurons.

  • Jarvie BC
  • J. Comp. Neurol.
  • 2012 Dec 1

Literature context:


Abstract:

Hypothalamic proopiomelanocortin (POMC) neurons have traditionally been defined by their peptide transmitters, which are important regulators of energy balance and reward. Recent work shows that POMC neurons can also release the amino acid transmitters γ-aminobutyric acid (GABA) and glutamate, although studying GABAergic and glutamatergic populations of POMC neurons has been hindered by the difficulty in reliably identifying amino acid (AA) transmitter phenotypes. In the present study, fluorescent in situ hybridization and immunohistochemistry were used to identify POMC neurons and to detect the presence of mRNA for the transporters responsible for packaging either GABA (vesicular GABA transporter [vGAT]) or glutamate (vesicular glutamate transporter [vGLUT]) into vesicles, as well as the enzymes responsible for GABA synthesis, glutamic acid decarboxylase (GAD)65 and GAD67. Approximately 7% of POMC neurons expressed vGlut2 and the highest percentage of vGlut2-positive POMC cells were located in the rostral arcuate nucleus. Despite the reports of GABA release from POMC neurons, vGat was not detected in POMC neurons, although Gad65 and Gad67 were present in ~40% of POMC neurons. Approximately half of the vGlut2-expressing POMC cells also expressed Gad65. Markers of neurotransmitter phenotype were better detected by using in situ hybridization techniques rather than transgenic expression of fluorophores under the control of the vGat or Gad67 promoters. It is now clear that the expression of markers of AA phenotype provides a useful means to identify distinct subpopulations of POMC neurons. Additionally, the method described will be useful to explore the possibility that plasticity of AA phenotype is an important aspect of POMC neuron function.

Funding information:
  • NIA NIH HHS - R21AG034264(United States)