Hundreds of millions of general anesthesia are performed each year on patients all over the world. Among these patients, 0.1-0.2% are victims of Accidental Awareness during General Anesthesia (AAGA), i.e., an unexpected awakening during a surgical procedure under general anesthesia. Although anesthesiologists try to closely monitor patients using various techniques to prevent this terrifying phenomenon, there is currently no efficient solution to accurately detect its occurrence. We propose the conception of an innovative passive brain-computer interface (BCI) based on an intention of movement to prevent AAGA. Indeed, patients typically try to move to alert the medical staff during an AAGA, only to discover that they are unable to. First, we examine the challenges of such a BCI, i.e., the lack of a trigger to facilitate when to look for an intention to move, as well as the necessity for a high classification accuracy. Then, we present a solution that incorporates Median Nerve Stimulation (MNS). We investigate the specific modulations that MNS causes in the motor cortex and confirm that they can be altered by an intention of movement. Finally, we perform experiments on 16 healthy participants to assess whether an MI-based BCI using MNS is able to generate high classification accuracies. Our results show that MNS may provide a foundation for an innovative BCI that would allow the detection of AAGA.

Prolonged exposure to general anesthesia (GA) results in long-lasting cognitive impairment, especially during critical stages of brain development. An exaggerated neuroinflammation induced by anesthesia is generally considered to be a key cause of cognitive impairment.

Children, after multiple exposures to general anesthesia, appear to be at an increased risk of developing learning disabilities. Almost all general anesthetics-including sevoflurane, which is commonly used for children-are potentially neurotoxic to the developing brain. Anesthesia exposure during development might also be associated with behavioral deficiencies later in life. To date, there is no treatment to prevent anesthesia-induced neurotoxicity and behavioral changes. In this study, we anesthetized 7-day-old neonatal mice with sevoflurane for 3 h per day for three consecutive days and found that the anesthesia led to mild behavioral abnormalities later in life that were detectable by using the novel object recognition test, Morris water maze, and fear conditioning test. Biochemical and immunohistochemical studies indicate that anesthesia induced a decrease in brain levels of postsynaptic density 95 (PSD95), a postsynaptic marker, and marked activation of neuronal apoptosis in neonatal mice. Importantly, insulin administered through intranasal delivery prior to anesthesia was found to prevent the anesthesia-induced long-term behavioral abnormalities, reduction of PSD95, and activation of neuronal apoptosis. These findings suggest that intranasal insulin administration could be an effective approach to prevent the increased risk of neurotoxicity and chronic damage caused by anesthesia in the developing brain.

In animal studies, prolonged sedation with general anesthetics has resulted in cognitive impairments that can last for days to weeks after exposure. One mechanism by which anesthesia may impair cognition is by decreasing adult hippocampal neurogenesis. Several studies have seen a reduction in cell survival after anesthesia in rodents with most studies focusing on two particularly vulnerable age windows: the neonatal period and old age. However, the extent to which sedation affects neurogenesis in young adults remains unclear. Adult neurogenesis in the dentate gyrus (DG) was analyzed in male and female rats 24 h after a 4-h period of sedation with isoflurane, propofol, midazolam, or dexmedetomidine. Three different cell populations were quantified: cells that were 1 week or 1 month old, labeled with the permanent birthdate markers EdU or BrdU, respectively, and precursor cells, identified by their expression of the endogenous dividing cell marker proliferating cell nuclear antigen (PCNA) at the time of sacrifice. Midazolam and dexmedetomidine reduced cell proliferation in the adult DG in both sexes but had no effect on postmitotic cells. Propofol reduced the number of relatively mature, 28-day old, neurons specifically in female rats and had no effects on younger cells. Isoflurane had no detectable effects on any of the cell populations examined. These findings show no general effect of sedation on adult-born neurons but demonstrate that certain sedatives do have drug-specific and sex-specific effects. The impacts observed on different cell populations predict that any cognitive effects of these sedatives would likely occur at different times, with propofol producing a rapid but short-lived impairment and midazolam and dexmedetomidine altering cognition after a several week delay. Taken together, these studies lend support to the hypothesis that decreased neurogenesis in the young adult DG may mediate the effects of sedation on cognitive function.

Cholinergic neurons in the basal forebrain (BF) have long been considered to be the key neurons in the regulation of cortical and behavioral arousal, and cholinergic activation in the downstream region of the BF can arouse anesthetized rats. However, whether the activation of BF cholinergic neurons can induce behavior and electroencephalogram (EEG) recovery from anesthesia is unclear. In this study, based on a transgenic mouse line expressing ChAT-IRES-Cre, we applied a fiber photometry system combined with GCaMPs expression in the BF and found that both isoflurane and propofol inhibit the activity of BF cholinergic neurons, which is closely related to the consciousness transition. We further revealed that genetic lesion of BF cholinergic neurons was associated with a markedly increased potency of anesthetics, while designer receptor exclusively activated by designer drugs (DREADD)-activated BF cholinergic neurons was responsible for slower induction and faster recovery of anesthesia. We also documented a significant increase in δ power bands (1-4 Hz) and a decrease in β (12-25 Hz) power bands in BF cholinergic lesioned mice, while there was a clearly noticeable decline in EEG δ power of activated BF cholinergic neurons. Moreover, sensitivity to anesthetics was reduced after optical stimulation of BF cholinergic cells, yet it failed to restore wake-like behavior in constantly anesthetized mice. Our results indicate a functional role of BF cholinergic neurons in the regulation of general anesthesia. Inhibition of BF cholinergic neurons mediates the formation of unconsciousness induced by general anesthetics, and their activation promotes recovery from the anesthesia state.

Propagating slow-waves in electroencephalogram (EEG) or local field potential (LFP) recordings occur during non-rapid eye-movement (NREM) sleep in both mammals and birds. Moreover, in both, input from the thalamus is thought to contribute to the genesis of NREM sleep slow-waves. Interestingly, the general features of slow-waves are also found under isoflurane anesthesia. However, it is unclear to what extent these slow-waves reflect the same processes as those giving rise to NREM sleep slow-waves. Similar slow-wave spatio-temporal properties during NREM sleep and isoflurane anesthesia would suggest that both types of slow-waves are based on related processes. We used a 32-channel silicon probe connected to a transmitter to make intra-cortical recordings of the visual hyperpallium in naturally sleeping and isoflurane anesthetized pigeons (Columba livia) using a within-bird design. Under anesthesia, the amplitude of LFP slow-waves was higher when compared to NREM sleep. Spectral power density across all frequencies (1.5-100 Hz) was also elevated. In addition, slow-wave coherence between electrode sites was higher under anesthesia, indicating higher synchrony when compared to NREM sleep. Nonetheless, the spatial distribution of slow-waves under anesthesia was more comparable to NREM sleep than to wake or REM sleep. Similar to NREM sleep, slow-wave propagation under anesthesia mainly occurred in the thalamic input layers of the hyperpallium, regions which also showed the greatest slow-wave power during both recording conditions. This suggests that the thalamus could be involved in the genesis of slow-waves under both conditions. Taken together, although slow-waves under isoflurane anesthesia are stronger, they share spatio-temporal activity characteristics with slow-waves during NREM sleep.

General anesthesia is a drug-induced reversible state comprised of altered states of consciousness, amnesia, analgesia, and immobility. The medial frontal cortex (mPFC) has been discovered to modulate the level of consciousness through cholinergic and glutamatergic pathways. The optogenetic tools combined with in vivo electrophysiological recording were used to study the neural oscillatory modulation mechanisms in mPFC underlying the loss of consciousness (LOC) and emergence. We found that optogenetic activation of both cholinergic and glutamatergic neurons in the basal forebrain (BF) reversed the hypnotic effect of propofol and accelerated the emergence from propofol-induced unconsciousness. The cholinergic light-activation during propofol anesthesia increased the power in the β (12-20 Hz) and low γ (20-30 Hz) bands. Conversely, glutamatergic activation increased the power at less specific broad (1-150 Hz) bands. The cholinergic-induced alteration to specific power bands after LOC had opposite effects to that of propofol. These results suggested that the cholinergic system might act on more specific cortical neural circuits related to propofol anesthesia.

Propofol is the most widely used intravenous general anesthetic; however, the neuronal circuits that mediate its anesthetic effects are still poorly understood. Glutamatergic neurons in the lateral hypothalamus have been reported to be involved in maintenance of arousal and consciousness. Using Vglut2-Cre transgenic mice, we recorded this group of cells specifically and found that propofol can directly inhibit the glutamatergic neurons, and enhance inhibitory synaptic inputs on these cells, thereby reducing neuronal excitability. Through chemogenetic interventions, we found that inhibition of these neurons increased the duration of propofol-induced anesthesia and reduced movement in the animals after the recovery of right reflex. In contrast, activating this group of cells reduced the duration of propofol anesthesia and increased the animals' locomotor activity after the recovery of right reflex. These results suggest that propofol-induced anesthesia involves the inhibition of glutamatergic neurons in the lateral hypothalamus.

While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care. In attempts to identify new analyses that discriminate clinically-relevant anesthesia timepoints, we tested 1/f frequency scaling as well as measures of complexity from nonlinear dynamics. Specifically, we tested whether analyses that characterize time-delayed embeddings, correlation dimension (CD), phase-space geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness changes in EEG activity. We performed these analyses on EEG activity collected from a traditionally hard-to-monitor patient population: geriatric patients on beta-adrenergic blockade who were anesthetized using a combination of fentanyl and propofol. We compared these analyses to traditional frequency-derived measures to test how well they discriminated EEG states before and after loss of response to verbal stimuli. We found spectral changes similar to those reported previously during loss of response. We also found significant changes in 1/f frequency scaling. Additionally, we found that our phase-space geometric characterization of time-delayed embeddings showed significant differences before and after loss of response, as did measures of MSE. Our results suggest that our new spectral and complexity measures are capable of capturing subtle differences in EEG activity with anesthesia administration-differences which future work may reveal to improve geriatric patient monitoring.

Deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN) under general anesthesia (GA) had been used in Parkinson's disease (PD) patients who are unable tolerate awake surgery. The effect of anesthetics on intraoperative microelectrode recording (MER) remains unclear. Understanding the effect of anesthetics on MER is important in performing STN DBS surgery with general anesthesia. In this study, we retrospectively performed qualitive and quantitative analysis of STN MER in PD patients received STN DBS with controlled desflurane anesthesia or LA and compared their clinical outcome. From January 2005 to March 2006, 19 consecutive PD patients received bilateral STN DBS surgery in Hualien Tzu-Chi hospital under either desflurane GA (n = 10) or LA (n = 9). We used spike analysis (frequency and modified burst index [MBI]) and the Hilbert transform to obtain signal power measurements for background and spikes, and compared the characterizations of intraoperative microelectrode signals between the two groups. Additionally, STN firing pattern characteristics were determined using a combined approach based on the autocorrelogram and power spectral analysis, which was employed to investigate differences in the oscillatory activities between the groups. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) before and after surgery. The results revealed burst firing was observed in both groups. The firing frequencies were greater in the LA group and MBI was comparable in both groups. Both the background and spikes were of significantly greater power in the LA group. The power spectra of the autocorrelograms were significantly higher in the GA group between 4 and 8 Hz. Clinical outcomes based on the UPDRS were comparable in both groups before and after DBS surgery. Under controlled light desflurane GA, burst features of the neuronal firing patterns are preserved in the STN, but power is reduced. Enhanced low-frequency (4-8 Hz) oscillations in the MERs for the GA group could be a characteristic signature of desflurane's effect on neurons in the STN.

Preoperative baseline cognitive impairment is associated with postoperative neurocognitive disorder (PND). Fasting, and more generally, calorie restriction has been shown to exert controversial effects in clinical settings and various animal models of neurological disorders. Every patient needs acute fasting before anesthesia and surgery. However, the impact of acute fasting on cognitive function remain largely unknown. We, therefore, set out to determine whether acute fasting can induce neurotoxicity and neurobehavioral deficits in rodents. In the present system establishment study, a mouse model of acute fasting was established. The effects of the acute fasting on natural and learned behavior were evaluated in the buried food test, open field test and the Y maze test. The expression of c-Fos, the marker of neuronal activation, and caspase-3 activation, the marker of cellular apoptosis, were measured with immunohistochemistry. We found that the 9 h acute fasting increased the latency to eat food in the buried food test. The acute fasting also selectively increased the total distance and decreased the freezing time in open field test, and increased the duration in the novel arm in the Y maze test. Besides, the immunohistochemical study showed that the fasting significantly increased the c-Fos level in the hippocampus and various sub-cortical areas, including paraventricular thalamus (PVT), dorsomedial hypothalamus (DMH), lateral hypothalamus (LH), and basal amygdala (BMA). However, the acute fasting did not induce apoptosis, demonstrating by no appearance of caspase-3 activation in the corresponding brain areas. These data showed that acute fasting did not cause cellular apoptosis and cognitive impairment in the mice. Instead, the acute fasting increased the neuronal activity, enhanced the ambulatory activity and improved the spatial recognition memory in the mice. These findings will promote more research in the established system to further determine the effects of perioperative factors on the postoperative neurocognitive function and the underlying mechanisms.

Patients with Alzheimer's disease show a sex-dependent decline of cognitive and behavioral performance. It is controversially discussed whether general anesthesia itself can aggravate or even cause this neurocognitive decline. Therefore, we investigated the effect of general anesthesia on neurocognitive and behavioral function and amyloidopathy in a mouse model of early-stage Alzheimer's disease with respect to sex.

Ethanol can induce acute stimulant responses in animals and human beings. Moreover, repeated exposure to ethanol may produce increased sensitivity to its acute locomotor stimulant actions, a process referred to as locomotor sensitization. The molecular mechanism of the development of acute stimulant responses and locomotor sensitization by ethanol is not fully understood. Sodium leak channel (NALCN) is widely expressed in central nervous system and controls the basal excitability of neurons. The present study aims to determine whether NALCN is implicated in the ethanol-induced acute responses and locomotor sensitization in mice. Here, our results showed that ethanol caused acute stimulant responses in DBA/2 mice. Locomotor sensitization was successfully induced following the sensitization procedure. Accordingly, the expression levels of NALCN mRNA and protein in the nucleus accumbens (NAc) were markedly increased in the sensitization mice compared to the control mice. Knockdown the expression levels of NALCN in the NAc alleviated both the ethanol-induced acute responses and locomotor sensitization. Our findings indicate that upregulation of NALCN expression in the NAc contributes to the ethanol-induced acute stimulant responses and locomotor sensitization in DBA/2 mice.

In animal experimentation, welfare and severity assessments of all procedures applied to animals are necessary to meet legal and ethical requirements, as well as public interests. So far, the methods suggested for this purpose are time consuming and personnel intensive. Also, evidence-based biostatistical methods for this purpose are still rare. We here tested whether the classification of heart rate (HR) and activity (Act) data monitored by telemetry in the home cage by unsupervised k-means-based class-labeling and subsequent Support Vector Machine (SVM) analysis allows severity assessment and grading of experimental procedures of different domains, including surgery, injection, behavioral testing, and routine handling for maintenance. Telemetric devices were subcutaneously implanted in young adult male Crl:CD(SD) and BDIX/UImHanZtm rats. After recovery, rats were randomly subjected to different experimental procedures, i.e., handling and cage change as routine maintenance, Rat Grimace Scale, burrowing, and social interaction for welfare assessment, as well as repeated subcutaneous injections. Thereafter, rats were either intracranially implanted with electrodes or injected with tumor cells. Directly after each procedure, HR and Act were monitored by telemetry in the home cage for 4 h. Application of k-means and SVM algorithms on the obtained data sets from baseline (as no stress), cage change (exploratory Act), and intracranial surgery (as burden) measurements computed three classes described as low HR/low Act, high HR/high Act, and high HR/low Act, respectively. Validation of the SVM model by entering data from all procedures confirmed the allocation to the high HR/low Act class (burden) after surgery, which lasted longer after subcutaneous transmitter implantation than after intracranial surgery. The majority of data points from repeated injections, behavioral testing, and maintenance handling were allocated to the low HR/low Act and high HR/high Act classes. Overall, the SVM model based on HR and Act data monitored in home cage after procedures may be useful for the classification and grading of experimental procedures of different domains.

Both mammals and birds exhibit two sleep states, slow wave sleep (SWS) and rapid eye movement (REM) sleep. Studying certain aspects of sleep-related electrophysiology in freely behaving animals can present numerous methodological constraints, particularly when even fine body movements interfere with electrophysiological signals. Interestingly, under light general anesthesia, mammals and birds also exhibit slow waves similar to those observed during natural SWS. For these reasons, slow waves occurring under general anesthesia are commonly used in the investigation of sleep-related neurophysiology. However, how spectral properties of slow waves induced by anesthesia correspond to those occurring during natural SWS in birds has yet to be investigated systematically. In this study, we systematically analyzed spectral properties of electroencephalographic (EEG) patterns of pigeons (Columba livia) occurring under two commonly used anesthetics, isoflurane and urethane. These data were compared with EEG patterns during natural sleep. Slow waves occurring during spontaneous SWS, and those induced with isoflurane and urethane all showed greatest absolute power in the slowest frequencies (<3 Hz). Isoflurane and urethane-induced slow waves had near-identical power spectra, and both had higher mean power than that observed during SWS for all frequencies examined (0-25 Hz). Interestingly, burst suppression EEG activity observed under deeper planes of isoflurane anesthesia could occur bihemispherically or unihemispherically. Electrophysiological patterns while under isoflurane and urethane share phenomenological and spectral similarities to those occurring during SWS, notably the generation of high amplitude, slow waves, and peak low-frequency power. These results build upon other studies which suggest that some anesthetics exert their effects by acting on natural sleep pathways. As such, anesthesia-induced slow waves appear to provide an acceptable model for researchers interested in investigating sleep-related slow waves utilizing electrophysiological methods not suitable for use in freely behaving birds.

Numerous studies have demonstrated that general anesthetics might damage the nervous system, thus, the effect of general anesthetics on the developing brain has attracted much attention. Dexmedetomidine (Dex) exhibits a certain neuroprotective effect, but the mechanism is obscure. In our study, pregnant rats on gestational day 20 (G20) were exposed to 3% sevoflurane for 2 h or 4 h, and the neuronal apoptosis in hippocampal CA1 region of the offspring rats was detected by quantification of TUNEL positive cells and cleaved-caspase3 (cl-caspase3). Different doses of Dex were intraperitoneally injected before sevoflurane anesthesia; then, the expression of apoptotic-related proteins including BCL-2, BAX and cl-caspase3 as well as amyloid precursor protein (APP, a marker of axonal injury), p-CRMP-2 and CRMP-2 were measured at postnatal days 0, 1and 3 (P0, P1, and P3, respectively). As an antagonist of the bone morphgenetic proteins (BMP) receptor, DMH1 was co-administered with sevoflurane plus Dex to investigate whether BMP/SMAD is associated with the neuroprotective effects of Dex. The results showed that prenatal sevoflurane anesthesia for 4 h activated apoptosis transiently, as manifested by the caspase3 activity peaked on P1 and disappeared on P3. In addition, the expressions of APP and p-CRMP-2/CRMP-2 in postnatal rat hippocampus were significantly increased, which revealed that prenatal sevoflurane anesthesia caused axonal injury of offspring. The long-term learning and memory ability of offspring rats was also impaired after prenatal sevoflurane anesthesia. These damaging effects of sevoflurane could be mitigated by Dex and DMH1 reversed the neuroprotective effect of Dex. Our results indicated that prenatal exposure to 3% sevoflurane for 4 h increased apoptosis and axonal injury, even caused long-term learning and memory dysfunction in the offspring rats. Dex dose-dependently reduced sevoflurane- anesthesia-induced the neurotoxicity by activating the BMP/SMAD signaling pathway.

Propofol is a worldwide-used intravenous general anesthetic with ideal effects, but hedonic effects of propofol have been reported and cause addictive issue. There is little known about the neurobiological mechanism of hedonic effects of propofol. Increasing researches have shown that the dopaminergic nervous system of the ventral tegmental area (VTA) and the noradrenergic system of locus coeruleus (LC) play a crucial role in hedonic experiences, which are putative sites for mediating the hedonic effects of propofol. In the present study, rat hedonic response scale and place conditioning paradigm were employed to examine the euphoric effects of propofol. In vivo GCaMP-based (AVV-hSyn-GCaMP6s) fiber photometry calcium imaging was used to monitor the real-time neuronal activity in VTA and LC area in rats exhibiting propofol-induced euphoric behaviors. Then DREADDs (designer receptors exclusively activated by designer drugs) modulation using rAAV-hSyn-hM4D(Gi)-EGFP was performed to confirm the neuronal substrate that mediates the euphoric effects of propofol. The score of hedonic facial responses was significantly increased in the 4 mg/kg group compared with that of the 0 mg/kg group. The locomotor activity in the propofol-paired compartment was significantly increased at the 4 mg/kg dose compared with that of the saline-paired group. When compared with the 0 mg/kg group, the place preference increased in the 4 mg/kg group. Administration of 4 mg/kg of propofol triggers reliable increases in GcaMP fluorescence. However, in the VTA GcaMP-expressing rats, administration of 4 mg/kg of propofol did not induce any change of GcaMP signals. The facial score and the place preference, which increased by 4 mg/kg propofol were abolished by chemogenetic inhibition of the neuronal activity in the LC area. Our results suggest that LC noradrenergic neurons, not VTA dopaminergic neurons, are directly involved in the hedonic effects of sub-anesthetic dose of propofol.

Neonatal and infant exposure to volatile anesthetics has been associated with long-term learning, memory, and behavioral deficits. Although early anesthesia exposure has been linked to a number of underlying structural abnormalities, functional changes associated with these impairments remain poorly understood. To investigate the relationship between functional alteration in neuronal circuits and learning deficiency, resting state functional MRI (rsfMRI) connectivity was examined in adolescent rabbits exposed to general anesthesia as neonates (1 MAC isoflurane for 2 h on postnatal days P8, P11, and P14) and unanesthetized controls before and after training with a trace eyeblink classical conditioning (ECC) paradigm. Long-range connectivity was measured between several key regions of interest (ROIs), including primary and secondary somatosensory cortices, thalamus, hippocampus, and cingulate. In addition, metrics of regional BOLD fluctuation amplitudes and coherence, amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were calculated. Our results showed that the trace ECC learning rate was significantly lower in the anesthesia-exposed group. No anesthesia-related changes in long-range connectivity, fALFF, or ReHo were found between any ROIs. However, ALFF was significantly higher in anesthesia-exposed rabbits in the primary and secondary somatosensory cortices, and ALFF in those areas was a significant predictor of the learning performance for trace ECC. The absence of anesthesia-related changes in long-range thalamocortical connectivity indicates that functional thalamocortical input is not affected. Higher ALFF in the somatosensory cortex may indicate the developmental disruption of cortical neuronal circuits after neonatal anesthesia exposure, including excessive neuronal synchronization that may underlie the observed cognitive deficits.

Electrical synapses between neurons exhibit a high degree of plasticity, which makes critical contributions to neuronal communication. The GABAergic parvalbumin-expressing (PV+) neurons in the thalamic reticular nucleus (TRN) interact with each other through electrical and chemical synapses. Plasticity of electrical synaptic transmission in TRN plays a key role in regulating thalamocortical and corticothalamic circuits and even the formation of consciousness. We here examined the effects of propofol, a commonly used general anesthetic agent, on the strength of electrical synapses between TRN PV+ neurons by fluorescence-guided patch-clamp recording and pharmacological methods. Results show that 100 μM propofol reduced the electrical synaptic strength between TRN PV+ neurons. Notably, the propofol-induced depression of electrical synaptic strength between TRN PV+ neurons was diminished by saclofen (10 μM, antagonist of GABAB receptors), but not blocked by gabazine (10 μM, antagonist of GABAA receptors). Application of baclofen (10 μM, agonist of GABAB receptors), similar to propofol, also reduced the electrical synaptic strength between TRN PV+ neurons. Moreover, the propofol-induced depression of electrical synaptic strength between TRN PV+ neurons was abolished by 9-CPA (100 μM, specific adenylyl cyclase inhibitor), and by KT5720 (1 μM, selective inhibitor of PKA). Our findings indicate that propofol acts on metabotropic GABAB receptors, resulting in a depression of electrical synaptic transmission of coupled TRN PV+ neurons, which is mediated by the adenylyl cyclase-cAMP-PKA signaling pathway. Our findings also imply that propofol may change the thalamocortical communication via inducing depression of electrical synaptic strength in the TRN.

Pre-clinical deep-brain stimulation (DBS) research has observed a growing interest in the use of portable stimulation devices that can be carried by animals. Not only can such devices overcome many issues inherent with a cable tether, such as twisting or snagging, they can also be utilized in a greater variety of arenas, including enclosed or large mazes. However, these devices are not inherently designed for water-maze environments, and their use has been restricted to individually-housed rats in order to avoid damage from various social activities such as grooming, playing, or fighting. By taking advantage of 3D-printing techniques, this study demonstrates an ultra-small portable stimulator with an environmentally-protective device housing, that is suitable for both social-housing and water-maze environments. The miniature device offers 2 channels of charge-balanced biphasic pulses with a high compliance voltage (12 V), a magnetic switch, and a diverse range of programmable stimulus parameters and pulse modes. The device's capabilities have been verified in both chronic pair-housing and water-maze experiments that asses the effects of nucleus reuniens DBS. Theta-burst stimulation delivered during a reference-memory water-maze task (but not before) had induced performance deficits during both the acquisition and probe trials of a reference memory task. The results highlight a successful application of 3D-printing for expanding on the range of measurement modalities capable in DBS research.