Posteromedial Nucleus Research Articles

Two Preputial Gland-Secreted Pheromones Evoke Sexually Dimorphic Neural Pathways in the Mouse Vomeronasal System.

Hexadecanol (16OH) and hexadecyl acetate (16Ac) are two pheromones secreted in a large quantity by mouse preputial glands and act on male and female mice differentially. Yet the underlying molecular and cellular mechanisms remain to be elucidated. In this study, we examined the activation of vomeronasal sensory neurons (VSNs) by these two pheromones and mapped the downstream neural circuits that process and relay their chemosignals. Using the calcium imaging method and immunohistochemistry, we found that a small number of VSNs were activated by 16OH, 16AC, or both in the male and female mice, most of which were located apically in the vomeronasal epithelium, and their numbers did not increase when the concentrations of 16OH and 16Ac were raised by 10,000-fold except that of female VSNs in response to 16OH. In the accessory olfactory bulb (AOB), the two pheromones evoked more c-Fos+ neurons in the anterior AOB (aAOB) than in the posterior AOB (pAOB); and the increases in the number of c-Fos+ neurons in both aAOB and pAOB were dose-dependent; and between sexes, the female AOB responded more strongly to 16OH than to 16Ac whereas the male AOB had the opposite response pattern. This sexual dimorphism was largely retained in the downstream brain regions, including the bed nucleus of the stria terminalis (BNST), the medial amygdaloid nucleus (MeA), the posteromedial cortical amygdaloid nucleus (PMCo), the medial preoptic area (MPA), and the ventromedial hypothalamic nucleus (VmH). Taken together, out data indicate that there is one V1r receptor each for 16OH, 16Ac, or both, and that activation of these receptors evokes sexually dimorphic neural circuits, directing different behavioral outputs and possibly modulating other pheromone-induced responses.

Effects of ketamine on voltage-gated sodium channels in the barrel cortex and the ventral posteromedial nucleus slices of rats.

Ketamine is commonly used as a dissociative anesthetic with unique actions in the central nervous system. Previous studies have found that the thalamocortical systems play an important role in general anesthetics induced unconsciousness. Whether the voltage-gated sodium channels in the thalamocortical systems are the target of ketamine remain unclear. The present study used a whole-cell patch-clamp technique to observe the effects of ketamine on voltage-gated Na channels in thalamocortical pyramidal neurons. We found that IC50 of ketamine on Na currents in the primary somatosensory barrel cortex pyramidal neurons and the thalamus ventral posteromedial nucleus pyramidal neurons was 686.72 ± 39.92 and 842.65 ± 87.28 μM, respectively. Ketamine accelerated the Na channels inactivation and slowed inactivation of Na channels after recovery but did not affect the activation. We demonstrated the detailed suppression process of neural voltage-gated Na channels by ketamine on thalamocortical slice. This may provide a new insight into the mechanical explanation for the ketamine anesthesia.

Recruitment of GABAergic Interneurons in the Barrel Cortex during Active Tactile Behavior

Neural computation involves diverse types of GABAergic inhibitory interneurons that are integrated with excitatory (E) neurons into precisely structured circuits. To understand how each neuron type shapes sensory representations, we measured firing patterns of defined types of neurons in the barrel cortex while mice performed an active, whisker-dependent object localization task. Touch excited fast-spiking (FS) interneurons at short latency, followed by activation of E neurons and somatostatin-expressing (SST) interneurons. Touch only weakly modulated vasoactive intestinal polypeptide-expressing (VIP) interneurons. Voluntary whisker movement activated FS neurons in the ventral posteromedial nucleus (VPM) target layers, a subset of SST neurons and a majority of VIP neurons. Together, FS neurons track thalamic input, mediating feedforward inhibition. SST neurons monitor local excitation, providing feedback inhibition. VIP neurons are activated by non-sensory inputs, disinhibiting E and FS neurons. Our data reveal rules of recruitment for interneuron types during behavior, providing foundations for understanding computation in cortical microcircuits.

Analysis on regional homogeneity of resting brain during balance acupuncture-induced analgesic effect in migraine patients without aura

To observe the relationship between the analgesic effect of balance acupuncture and functional changes in brain in patients with migraine without aura. A total of 40 cases of migraine without aura were equally randomized into a headache-acupoint group and a sham-acupoint group. When acupuncture given, a filiform needle was inserted into the headache-acupoint (the midpoint of the depression region anterior to the juncture of the first and second metatarsal bones on the dorsum of the foot) or the sham point (the midpoint of the depression region anterior to the juncture site between the 3rd and 4th metatarsal joints of the dorsum of the foot) about 25-40 mm deep and manipulated for a while till the patient experienced feelings of electric shock and numbness, then withdrawn immediately. The treatment was conducted once daily for 4 weeks. The visual analogue scale (VAS) was used to evaluate the severity of pain, and the regional homogeneity (ReHo) analysis of resting state functional magnetic resonance imaging (fMRI) was used to assess changes of the spontaneous brain activity. After acupuncture, the analgesic effect of headache-acupoint was better than that of the sham-acupoint in both intervention stage and the follow-up stage (P< 0.05), and was also stronger in the intervention stage than in the follow-up stage (P<0.05). There was no significant difference in the analgesic effect between the intervention stage and the follow-up stage in the sham-acupoint group (P>0.05). Compared with pre-intervention, 4-weeks' intervention at the headache-acupoint showed an increase of ReHo values in the anterior cingulate gyrus, anterior central gyrus, superior orbital frontal gyrus, insula, inferior lobule, left anterior cingulate gyrus, ventral lateral nucleus and ventral posteromedial nucleus of the thalamus, pontine nucleus, cerebellar tonsils and orbital frontal inferior gyrus of the brain (P<0.05), and a decrease of ReHo values in the right brain bridge, central posterior gyrus, posterior cingulate gyrus, left central anterior gyrus, posterolateral nucleus of thalamus, and hippocampus (P<0.05), separately. In the sham-acupoint group, the ReHo value was increased in the right tongue gyrus, the left anterior lobe, the anterior cingulate gyrus and the lower occipital gyrus of the brain (P<0.05), and reduced in the left ventral posterolateral nucleus of the thalamus, separately (P<0.05). Balance acupuncture stimulation of headache acupoint has an analgesic effect in migraine patients without aura, which may be related to its effect in regulating resting state brain function of the limbic-system-dominated multiple brain regions.

Positive correlation between blood glucose and radiotherapy doses to the central gustatory system in Glioblastoma Multiforme patients

BackgroundThe aim of this study was to assess the correlations between the levels of blood glucose (BG) and the dose of radiation therapy (RT) to the central gustatory system (GS) in glioblastoma multiforme (GBM) patients.MethodsThirty-seven GBM patients with regular blood glucose measurements were investigated retrospectively. 59.5% were female and 40.5% male with a median age of 64.3 years (range 27.4–85.6). Diabetes mellitus type 2 (DM2) history, BG levels and dexamethasone (DEXA) medication were assessed. The analyzed central gustatory structures were: solitary tract and nucleus, ventral posteromedial nucleus of the thalamus, sensory tongue area of the postcentral gyrus, anterior part of the insula, frontal operculum, amygdala, hypothalamus. These structures were delineated on magnetic resonance tomographies (MRIs) registered to planning-CTs. All GS doses were transformed in equivalent doses in 2 Gy fraction (EQD2).ResultsTwenty one patients (56.8%) had at least one BG values over 200 mg/dl during RT. There was a difference between average BG in DM2: 192.8 mg/dl (±24.4) and non-DM2 patients: 145.7 mg/dl (±39.5; p = 0.01) but no significant difference in daily DEXA medication – DM2 patients: 7.9 mg/d (±1.9) vs. non-DM2: 9.3 mg/dl (±5.7; p = 0.29). The EQD2 Dmean to the total GS was 36.0Gy (±8.6 Gy). There was a tendency for a higher increase in maximum BG values with more radiation dose to the total GS (b = 1.9, R2 = 0.103, p = 0.06).ConclusionBG levels in GBM patients are in direct correlation to the dose of RT applied to the central GS. GBM patients that undergo RT should thus be closely monitored for changes in BG levels during and after the radiation.

Stereological Investigation of the Rat Ventral Thalamic Nuclei Following Developmental Hyperserotonemia

Elevated blood serotonin in perinatal development is the most consistent neurochemical finding reported in Autism Spectrum Disorder (ASD), and has been implicated in the pathogenesis of the disorder. Accordingly, pre- and postnatal administration of the non-selective serotonin agonist, 5-methoxytryptamine (5-MT), is hypothesized as a model of developmental hyperserotonemia (DHS) to investigate the behavioral and morphological implications in ASD. Our previous study, examining the effects of DHS, found significant neuroanatomical changes in the dendritic architecture and connectivity of neurons in the dentate nucleus of the cerebellum. The present investigation has gone further to describe alterations in the development of the dentate-thalamo-cortical pathway, a neural network involved in motor learning, automaticity of movements, and higher cognitive functions affected in ASD. Using unbiased stereological techniques, serial sections of DHS rats were compared to age-matched controls. Analysis was performed on nuclear volume, estimated cell number, area, distribution, and volume within the principle nuclei of the thalamus. While results did not show a change in the overall volume of the thalamus, when grouped by estimated total brain volume, the mean thalamic volume was significantly reduced in the DHS group relative to controls. Additionally, significant reductions in cell numbers, density and distribution were observed in subdivisions of the principle nuclei including the ventral anterior, ventral lateral, ventral posterolateral, and ventral posteromedial nuclei. Alterations in these areas and their reciprocal connections throughout the brain may effect neuronal organization and be implicated in the neuropathological and behavioral changes observed in ASD.

Collateral Projections from the Medullary Dorsal Horn to the Ventral Posteromedial Thalamic Nucleus and the Parafascicular Thalamic Nucleus in the Rat

Medullary dorsal horn (MDH), the homolog of spinal dorsal horn, plays essential roles in processing of nociceptive signals from orofacial region toward higher centers, such as the ventral posteromedial thalamic nucleus (VPM) and parafascicular thalamic nucleus (Pf), which belong to the sensory-discriminative and affective aspects of pain transmission systems at the thalamic level, respectively. In the present study, in order to provide morphological evidence for whether neurons in the MDH send collateral projections to the VPM and Pf, a retrograde double tracing method combined with immunofluorescence staining for substance P (SP), SP receptor (SPR) and Fos protein was used. Fluoro-gold (FG) was injected into the VPM and the tetramethylrhodamine-dextran (TMR) was injected into the Pf. The result revealed that both FG- and TMR-labeled projection neurons were observed throughout the entire extent of the MDH, while the FG/TMR double-labeled neurons were mainly located in laminae I and III. It was also found that some of the FG/TMR double-labeled neurons within lamina I expressed SPR and were in close contact with SP-immunoreactive (SP-ir) terminals. After formalin injection into the orofacial region, 41.4% and 34.3% of the FG/TMR double-labeled neurons expressed Fos protein in laminae I and III, respectively. The present results provided morphological evidence for that some SPR-expressing neurons within the MDH send collateral projections to both VPM and Pf and might be involved in sensory-discriminative and affective aspects of acute orofacial nociceptive information transmission.

Thalamic Drive of Cortical Parvalbumin-Positive Interneurons during Down States in Anesthetized Mice

SummaryUp and down states are among the most prominent features of the thalamo-cortical system during non-rapid eye movement (NREM) sleep and many forms of anesthesia. Cortical interneurons, including parvalbumin (PV) cells, display firing activity during cortical down states, and this GABAergic signaling is associated with prolonged down-state durations. However, what drives PV interneurons to fire during down states remains unclear. We here tested the hypothesis that background thalamic activity may lead to suprathreshold activation of PV cells during down states. To this aim, we performed two-photon guided juxtasomal recordings from PV interneurons in the barrel field of the somatosensory cortex (S1bf) of anesthetized mice, while simultaneously collecting the local field potential (LFP) in S1bf and the multi-unit activity (MUA) in the ventral posteromedial (VPM) thalamic nucleus. We found that activity in the VPM was associated with longer down-state duration in S1bf and that down states displaying PV cell firing were associated with increased VPM activity. Moreover, thalamic inhibition through application of muscimol reduced the fraction of spikes discharged by PV cells during cortical down states. Finally, we inhibited PV interneurons using optogenetics during down states while monitoring cortical LFP under control conditions and after thalamic muscimol injection. We found increased latency of the optogenetically triggered down-to-up transitions upon thalamic pharmacological blockade compared to controls. These findings demonstrate that spontaneous thalamic activity inhibits cortex during down states through the activation of PV interneurons.

Differential activation of ascending noxious pathways associated with trigeminal nerve injury.

Trigeminal spinal subnucleus caudalis (Vc) neurons that project to the ventral posteromedial thalamic nucleus (VPM) and parabrachial nucleus (PBN) are critical for orofacial pain processing. We hypothesized that persistent trigeminal nerve injury differentially alters the proportion of Vc neurons that project to VPM and PBN in a modality-specific manner. Neuroanatomical approaches were used to quantify the number of Vc neurons projecting to VPM or PBN after chronic constriction injury of the infraorbital nerve (ION-CCI) and subsequent upper-lip stimulation. Male rats received injections of retrograde tracer fluorogold into the contralateral VPM or PBN on day 7 after ION-CCI, and at 3 days after that, either capsaicin injection or noxious mechanical stimulation was applied to the upper lip ipsilateral to nerve injury. Infraorbital nerve chronic constriction injury rats displayed greater forelimb wiping to capsaicin injection and mechanical allodynia of the lip than sham rats. Total cell counts for phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons after capsaicin or mechanical lip stimuli were higher in ION-CCI than sham rats as was the percentage of pERK-IR PBN projection neurons. However, the percentage of pERK-IR VPM projection neurons was also greater in ION-CCI than sham rats after capsaicin but not mechanical lip stimuli. The present findings suggest that persistent trigeminal nerve injury increases the number of Vc neurons activated by capsaicin or mechanical lip stimuli. By contrast, trigeminal nerve injury modifies the proportion of Vc nociceptive neurons projecting to VPM and PBN in a stimulus modality-specific manner and may reflect differential involvement of ascending pain pathways receiving C fiber and mechanosensitive afferents.

Ratbot navigation using deep brain stimulation in ventral posteromedial nucleus

ABSTRACT Deep Brain Stimulation (DBS) is a medical-practical method and has been applied to solve many medical complications. Animal usage as sensors and actuators, mind-controlled machines, and animal navigation are some of the non-medical DBS applications. One of the brain areas used in ratbot navigation is the Ventral Posteromedial Nucleus (VPM), which creates non-volunteer head rotation. Rat training by water/food restriction can be used to create forward movement. In this study, a combination of VPM stimulation and water/food restriction has been employed to establish a complete navigation system. Five rats responded to VPM stimulations. However, with three of them, rats rotated to the same direction after the stimulations of either VPM side of the brain. Two rats rotated bilaterally, proportionate to the VPM stimulation side. These two rats were trained in a T-shape maze and became ratbots. The results of the 3-session test showed that their navigation performances were 96% and 86%, respectively. These ratbots are suitable for navigational purposes and are ready to complete the missions that are dangerous or impossible for humans.

Block Face Scanning Electron Microscopy of Fluorescently Labeled Axons Without Using Near Infra-Red Branding.

In this article, we describe the method that allows fluorescently tagged structures such as axons to be targeted for electron microscopy (EM) analysis without the need to convert their labels into electron dense stains, introduce any fiducial marks, or image large volumes at high resolution. We optimally preserve and stain the brain tissue for ultrastructural analysis and use natural landmarks, such as cell bodies and blood vessels, to locate neurites that had been imaged previously using confocal microscopy. The method relies on low and high magnification views taken with the light microscope, after fixation, to capture information of the tissue structure that can later be used to pinpoint the position of structures of interest in serial EM images. The examples shown here are td Tomato expressing cortico-thalamic axons in the posteromedial nucleus of the mouse thalamus, imaged in fixed tissue with confocal microscopy, and subsequently visualized with serial block-face EM (SBEM) and reconstructed into 3D models for analysis.

A 0.13-&lt;inline-formula&gt; &lt;tex-math notation="LaTeX"&gt;$\mu\text{m}$ &lt;/tex-math&gt; &lt;/inline-formula&gt; CMOS SoC for Simultaneous Multichannel Optogenetics and Neural Recording

This paper presents a 0.13- $\mu \text{m}$ CMOS system-on-chip (SoC) for simultaneous multichannel optogenetics and multichannel neural recording in freely moving laboratory animals. This fully integrated system provides 10 multimodal recording channels with analog-to-digital conversion and a four- channel LED driver circuit for optogenetic stimulation. The bio-amplifier design includes a programmable bandwidth (BW) (0.5 Hz–7 kHz) to collect either the action potentials (APs) and/or the local field potentials (LFPs) and has a noise efficiency factor (NEF) of 2.30 for an input-referred noise of 3.2 $\mu V_{\text {rms}}$ within a BW of 10–7 kHz. The low-power delta–sigma ( $\Delta \Sigma $ ) MASH 1-1-1 analog-to-digital converter (ADC) is designed to work at low oversampling ratios (OSRs) (≤50) and has an effective number of bits (ENOB) of 9.75 bits at an OSR of 25 (BW of 10 kHz). The utilization of a $\Delta \Sigma $ ADC is the key to address the flexibility needed to address different noise versus power consumption tradeoff of various experimental settings. It leverages a new technique that reduces its size by subtracting the output of each $\Delta \Sigma $ branch in the digital domain, instead of in the analog domain as done conventionally. The ADC is followed by an on-chip fourth-order cascaded integrator-comb (CIC4) decimation filter (DF). A whole recording channel, including the bio-amplifier, the $\Delta \Sigma $ MASH 1-1-1, and the DF consumes 11.2 $\mu \text{W}$ . Optical stimulation is performed with an LED driver using a regulated cascode current source with feedback that can accommodate a wide range of LED parameters and battery voltages. The SoC is validated in vivo within a wireless experimental platform in both the ventral posteromedial nucleus (VPM) and cerebral motor cortex brain regions of a virally mediated Channelrhodopsin-2 (ChR2) rat.

Multisensory integration in rodent tactile but not visual thalamus

Behavioural performance requires a coherent perception of environmental features that address multiple senses. These diverse sensory inputs are integrated in primary sensory cortices, yet it is still largely unknown whether their convergence occurs even earlier along the sensory tract. Here we investigate the role of putatively modality-specific first-order (FO) thalamic nuclei (ventral posteromedial nucleus (VPM), dorsal lateral geniculate nucleus (dLGN)) and their interactions with primary sensory cortices (S1, V1) for multisensory integration in pigmented rats in vivo. We show that bimodal stimulation (i.e. simultaneous light flash and whisker deflection) enhances sensory evoked activity in VPM, but not dLGN. Moreover, cross-modal stimuli reset the phase of thalamic network oscillations and strengthen the coupling efficiency between VPM and S1, but not between dLGN and V1. Finally, the information flow from VPM to S1 is enhanced. Thus, FO tactile, but not visual, thalamus processes and relays sensory inputs from multiple senses, revealing a functional difference between sensory thalamic nuclei during multisensory integration.

The time course of blood brain barrier leakage and its implications on the progression of methamphetamine-induced seizures

The initial goals of these experiments were to determine: 1) if blood-brain barrier (BBB) breakdown was a cause or an effect of METH-induced seizures; 2) all the brain regions where BBB is disrupted as seizures progress; and 3) the correlations between body temperature and vascular leakage and neurodegeneration. A fourth objective was added after initial experimentation to determine if sub-strain differences existed in adult male C57 B6 J (Jackson laboratories, JAX) versus C57 B6N (Charles River, CR) mice involving their susceptibility to BBB breakdown and seizure severity. With the 1st “maximal” intensity myoclonic-tonic seizure (MCT) varying degrees of IgG infiltration across the BBB (≤1 mm2) were prominent in olfactory system (OS) associated regions and in thalamus, hypothalamus and neocortex. IgG infiltration areas in the OS-associated regions of the bed nucleus of the stria terminalis, septum and more medial amygdala nuclei, and the hypothalamus were increased significantly by the time continuous behavioral seizures (CBS) developed. Mice receiving METH that had body temperatures of ≥40 °C had IgG infiltration along with MCT or CBS but peak body temperatures above 40 °C did not significantly increase IgG infiltration. Neurodegeneration seen at ≥6 h was restricted to the OS in both JAX and CR mice and was most prominent in the posteromedial cortical amygdaloid nucleus. Neurodegeneration in the anterior septum (tenia tecta) was seen only in the JAX mice. We hypothesize that METH-induced hypertension and hyperthermia lead to BBB breakdown and other vascular dysfunctions in the OS brain regions resulting in OS hyperexcitation. Excitation of the OS neural network then leads to the development of seizures. These seizures in turn exacerbate the energy depletions and the reactive oxygen stress produced by hyperthermia further damaging the BBB and vascular function. These events form a recurrent cycle that results in ever increasing seizure activity and neurotoxicity.

Cortical and Subcortical Projections from Granular Insular Cortex Receiving Orofacial Proprioception

We have recently revealed that the proprioceptive signal from jaw-closing muscle spindles (JCMSs) is conveyed to the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of secondary somatosensory cortex (dGIrvs2) via the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM) in rats. However, it remains unclear to which cortical or subcortical structures the JCMS proprioceptive information is subsequently conveyed from the dGIrvs2. To test this issue, we injected an anterograde tracer, biotinylated dextranamine, into the electophysiologically identified dGIrvs2, and analyzed the resultant distribution profiles of labeled axon terminals in rats. Labeled terminals were distributed with an ipsilateral predominance. In the cerebral cortex, they were seen in the primary and secondary somatosensory cortices, lateral and medial agranular cortices and dorsolateral orbital cortex. In the basal ganglia, they were found in the caudate putamen, core part of accumbens nucleus, lateral globus pallidus, subthalamic nucleus, and substantia nigra pars compacta and pars reticulata. They were also observed in the central amygdaloid nucleus and extended amygdala (the interstitial nucleus of posterior limb of anterior commissure and the juxtacapsular part of lateral division of bed nucleus of stria terminalis). In the thalamus, they were seen in the reticular nucleus, ventromedial nucleus, core VPM, parvicellular part of ventral posterior nucleus, oval paracentral nucleus, medial and triangular parts of posterior nucleus, and zona incerta as well as the VPMcvm. These data suggest that the JCMS proprioceptive information through the dGIrvs2 is transmitted to the emotional ‘limbic’ regions as well as sensorimotor regions.

Deep brain stimulation for intractable neuropathic facial pain.

OBJECTIVE Deep brain stimulation (DBS) is a well-established, evidence-based therapy with FDA approval for Parkinson's disease and essential tremor. Despite the early successful use of DBS to target the sensory thalamus for intractable facial pain, subsequent studies pursuing various chronic pain syndromes reported variable efficacy, keeping DBS for pain as an investigational and "off-label" use. The authors report promising results for a contemporary series of patients with intractable facial pain who were treated with DBS. METHODS Pain outcomes for 7 consecutive patients with unilateral, intractable facial pain undergoing DBS of the ventral posteromedial nucleus of the thalamus (VPM) and the periaqueductal gray (PAG) were retrospectively reviewed. Pain was assessed preoperatively and at multiple postoperative time points using the visual analog scale (VAS), the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), and the Pain Disability Index (PDI). RESULTS VAS scores significantly decreased from a mean ± SD of 9.0 ± 1.3 preoperatively to 2.6 ± 1.5 at 1 year postoperatively (p = 0.001). PDI scores decreased from a mean total of 48.5 to 28.5 (p = 0.01). SF-MPQ-2 scores decreased from a mean of 4.6 to 2.4 (p = 0.03). Notably, several patients did not experience maximum improvement until 6-9 months postoperatively, correlating with repeated programming adjustments. CONCLUSIONS DBS of the VPM and PAG is a potential therapeutic option for patients suffering from severe, intractable facial pain refractory to other interventions. Improved efficacy may be observed over time with close follow-up and active DBS programming adjustments.

Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders

The psychopathology of depression is highly complex and the outcome of studies on animal models is divergent. In order to find brain regions that could be metabolically distinctively active across a variety of mouse depression models and to compare the interconnectivity of brain regions of wild-type and such genetically modified mice, histochemical mapping of oxidative metabolism was performed by the measurement of cytochrome oxidase activity. We included mice with the heterozygous knockout of the vesicular glutamate transporter (VGLUT1−/+), full knockout of the cannabinoid 1 receptor (CB1−/−), an anti-sense knockdown of the glucocorticoid receptor (GRi) and overexpression of the human 5-hydroxytryptamine transporter (h5-HTT). Altogether 76 mouse brains were studied to measure oxidative metabolism in one hundred brain regions, and the obtained dataset was submitted to a variety of machine learning algorithms and multidimensional scaling. Overall, the top brain regions having the largest contribution to classification into depression model were the lateroanterior hypothalamic nucleus, the anterior part of the basomedial amygdaloid nucleus, claustrum, the suprachiasmatic nucleus, the ventromedial hypothalamic nucleus, and the anterior hypothalamic area. In terms of the patterns of inter-regional relationship between wild-type and genetically modified mice there was little overall difference, while the most deviating brain regions were cortical amygdala and ventrolateral and ventral posteromedial thalamic nuclei. The GRi mice that most clearly differed from their controls exhibited deviation of connectivity for a number of brain regions, such as ventrolateral thalamic nucleus, the intermediate part of the lateral septal nucleus, the anteriodorsal part of the medial amygdaloid nucleus, the medial division of the central amygdaloid nucleus, ventral pallidum, nucleus of the vertical limb of the diagonal band, anteroventral parts of the thalamic nucleus and parts of the bed nucleus of the stria terminalis. Conclusively, the GRi mouse model was characterized by changes in the functional connectivity of the extended amygdala and stress response circuits.

Regulation of cortical activity and arousal by the matrix cells of the ventromedial thalamic nucleus

The “non-specific” ventromedial thalamic nucleus (VM) has long been considered a candidate for mediating cortical arousal due to its diffuse, superficial projections, but direct evidence was lacking. Here, we show in mice that the activity of VM calbindin1-positive matrix cells is high in wake and REM sleep and low in NREM sleep, and increases before cortical activity at the sleep-to-wake transition. Optogenetic stimulation of VM cells rapidly awoke all mice from NREM sleep and consistently caused EEG activation during slow wave anesthesia, while arousal did not occur from REM sleep. Conversely, chemogenetic inhibition of VM decreased wake duration. Optogenetic activation of the “specific” ventral posteromedial nucleus (VPM) did not cause arousal from either NREM or REM sleep. Thus, matrix cells in VM produce arousal and broad cortical activation during NREM sleep and slow wave anesthesia in a way that accounts for the effects classically attributed to “non-specific” thalamic nuclei.

Amygdala Corticofugal Input Shapes Mitral Cell Responses in the Accessory Olfactory Bulb.

Interconnections between the olfactory bulb and the amygdala are a major pathway for triggering strong behavioral responses to a variety of odorants. However, while this broad mapping has been established, the patterns of amygdala feedback connectivity and the influence on olfactory circuitry remain unknown. Here, using a combination of neuronal tracing approaches, we dissect the connectivity of a cortical amygdala [posteromedial cortical nucleus (PmCo)] feedback circuit innervating the mouse accessory olfactory bulb. Optogenetic activation of PmCo feedback mainly results in feedforward mitral cell (MC) inhibition through direct excitation of GABAergic granule cells. In addition, LED-driven activity of corticofugal afferents increases the gain of MC responses to olfactory nerve stimulation. Thus, through corticofugal pathways, the PmCo likely regulates primary olfactory and social odor processing.

S117. Intraoperative detection of posterior circulation transient ischemic attack: Single case study

Introduction Intraoperative Neuromonitoring (IONM) has been utilized to aid in the prevention of iatrogenic injury. Studies have described the role IONM may play in predicting post procedural neurological deficits (PPNDs). Here we discuss a unique case study of a patient who underwent stent-assisted embolization of a large basilar tip aneurysm with very specific localizing changes observed by analysis of somatosensory evoked potentials (SSEPs), electroencephalography (EEG), and brainstem auditory evoked potentials (BAEPs). Methods A 66 year old female with past medical history of hypertension and hyperlipidemia presented to the emergency department (ED) with photophobia and a left dilated pupil. MR angiography revealed a large basilar tip aneurysm. Aspirin and Plavix were administered and a stent-assisted coil embolization was performed with complete resolution of symptoms. Follow-up elective repair of the aneurysm was scheduled. Prior to the follow-up elective repair, the patient presented to the ED once again with a new onset headache and anisocoria. MR angiogram was performed which revealed no acute changes. The patient was admitted and underwent further embolization of the aneurysm from the left P1 into the basilar apex. The initial stent was deployed with no complications. During advancement of a second stent, abrupt cortical amplitude decreases of 76% and 79% in the left upper and lower extremity traces, respectively, were observed. All other traces remained stable. Catheter placement was inspected and noted as normal. Signals began to improve and returned to baseline in less than 10 min as the procedure was completed without placement of an additional stent. Results Six days post-operatively, the patient presented to an outside ED complaining of posterior headache and left-sided paresthesia in the trigeminal nerve distribution. She was transferred to the University of Michigan for further evaluation. MR imaging was unremarkable but further workup revealed sub-therapeutic Plavix levels so her dose was increased. Her symptoms resolved within 24 h. Conclusion We hypothesize that both intraoperative electrophysiological changes and PPNDs reflect a specific ischemic event in the P1/P2 deep perforator distribution affecting the right ventral posterolateral and posteromedial nuclei of the thalamus, respectively. This case highlights the potential anatomic specificity of multimodal IONM by the changes seen at the time of manipulation of the perforating branches of the posterior circulation, correlating with subsequent TIA and symptoms attributable to the same vascular distribution. This interpretation must be taken with caution as this does not establish a direct correlation of IONM changes with subsequent TIA. Potential correlation should be studied in a larger population undergoing endovascular intervention in the posterior circulation.