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The parasubthalamic nucleus (PSTN), a small nucleus located on the lateral edge of the posterior hypothalamus, has emerged in recent years as a highly interconnected node within the network of brain regions sensing and regulating autonomic function and homeostatic needs. Furthermore, the strong integration of the PSTN with extended amygdala circuits makes it ideally positioned to serve as an interface between interoception and emotions. While PSTN neurons are mostly glutamatergic, some of them also express neuropeptides that have been associated with stress-related affective and motivational dysfunction, including substance P, corticotropin-releasing factor, and pituitary adenylate-cyclase activating polypeptide. PSTN neurons respond to food ingestion and anorectic signals, as well as to arousing and distressing stimuli. Functional manipulation of defined pathways demonstrated that the PSTN serves as a central hub in multiple physiologically relevant networks and is notably implicated in appetite suppression, conditioned taste aversion, place avoidance, impulsive action, and fear-induced thermoregulation. We also discuss the putative role of the PSTN in interoceptive dysfunction and negative urgency. This review aims to synthesize the burgeoning preclinical literature dedicated to the PSTN and to stimulate interest in further investigating its influence on physiology and behavior., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Synapses are able to form in the absence of neuronal activity, but how is their subsequent maturation affected in the absence of regulated vesicular release? We explored this question using 3D electron microscopy and immunoelectron microscopy analyses in the large, complex synapses formed between cortical sensory efferent axons and dendrites in the posterior thalamic nucleus. Using a Synaptosome-associated protein 25 conditional knockout (Snap25 cKO), we found that during the first 2 postnatal weeks the axonal boutons emerge and increase in the size similar to the control animals. However, by P18, when an adult-like architecture should normally be established, axons were significantly smaller with 3D reconstructions, showing that each Snap25 cKO bouton only forms a single synapse with the connecting dendritic shaft. No excrescences from the dendrites were formed, and none of the normally large glomerular axon endings were seen. These results show that activity mediated through regulated vesicular release from the presynaptic terminal is not necessary for the formation of synapses, but it is required for the maturation of the specialized synaptic structures between layer 5 corticothalamic projections in the posterior thalamic nucleus., (© The Author(s) 2020. Published by Oxford University Press.)

Functional peculiarities of paralemniscal subdivision of the thalamocortical system were examined in normal Wistar and in WAG/Rij rats genetically prone to absence epilepsy. In 6-7-month-old WAG/Rij characterized by developed epileptic activity, the response of cortical somatosensory neurons to single electrical stimulation of the posterior thalamic nucleus was phasic, whereas in normal Wistar rats, similar reaction was tonic. The study views this phasic response as neural equivalent of spike-wave discharges known as typical EEG symptom of absence epilepsy.

Critically important components of the maternal neural circuit in the preoptic area robustly activated by suckling were recently identified. In turn, suckling also contributes to hormonal adaptations to motherhood, which includes oxytocin release and consequent milk ejection. Other reproductive or social stimuli can also trigger the release of oxytocin centrally, influencing parental or social behaviors. However, the neuronal pathways that transfer suckling and other somatosensory stimuli to the preoptic area and oxytocin neurons have been poorly characterized. Recently, a relay center of suckling was determined and characterized in the posterior intralaminar complex of the thalamus (PIL). Its neurons containing tuberoinfundibular peptide 39 project to both the preoptic area and oxytocin neurons in the hypothalamus. The present review argues that the PIL is a major relay nucleus conveying somatosensory information supporting maternal behavior and oxytocin release in mothers, and may be involved more generally in social cue evoked oxytocin release, too., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The posterior nucleus of thalamus (PO) is a higher-order nucleus involved in sensorimotor processing, including nociception. An important characteristic of PO is its wide range of activity profiles that vary across states of arousal, thought to underlie differences in somatosensory perception subject to attention and degree of consciousness. Furthermore, PO loses the ability to downregulate its activity level in some forms of chronic pain, suggesting that regulatory mechanisms underlying the normal modulation of PO activity may be pathologically altered. However, the mechanisms responsible for regulating such a wide dynamic range of activity are unknown. Here, we test a series of hypotheses regarding the function of several presynaptic receptors on both GABAergic and glutamatergic afferents targeting PO in mouse, using acute slice electrophysiology. We found that presynaptic GABA B receptors are present on both GABAergic and glutamatergic terminals in PO, but only those on GABAergic terminals are tonically active. We also found that release from GABAergic terminals, but not glutamatergic terminals, is suppressed by cholinergic activation and that a subpopulation of GABAergic terminals is regulated by cannabinoids. Finally, we discovered the presence of tonic currents mediated by extrasynaptic GABA A receptors in PO that are heterogeneously distributed across the nucleus. Thus we demonstrate that multiple regulatory mechanisms concurrently exist in PO, and we propose that regulation of inhibition, rather than excitation, is the more consequential mechanism by which PO activity can be regulated. NEW & NOTEWORTHY The posterior nucleus of thalamus (PO) is a key sensorimotor structure, whose activity is tightly regulated by inhibition from several nuclei. Maladaptive plasticity in this inhibition leads to severe pathologies, including chronic pain. We reveal here, for the first time in PO, multiple regulatory mechanisms that modulate synaptic transmission within PO. These findings may lead to targeted therapies for chronic pain and other disorders., (Copyright © 2017 the American Physiological Society.)

Central pain is one of the most important complications after spinal cord injury (SCI), and thereby, its treatment raises many challenges. After SCI, in a cascade of molecular events, a marked increase in glutamate at the injury site results in secondary changes which may impact on supraspinal regions, mainly ventroposterolateral (VPL). There is little information about the changes in glutamate metabolism in the VPL and whether it contributes to SCI-related central pain. The present study was performed to evaluate glutamate release in the VPL following electrolytic lesion of spinothalamic tract (STT). A laminectomy was performed at spinal segments of T9-T10 in male rats, and then, unilateral electrolytic lesions were made in the STT. Glutamate concentrations in ipsilateral VPL dialysate were measured by HPLC method at days 3, 7, 14, 21 and 28 post-injury. Tactile pain and motor activity were also examined. Glutamate levels were significantly increased in ipsilateral VPL of spinal-cord-injured rats 2 weeks after SCI and remained high up to day 28 post-surgery. The STT lesions had no marked effect on our measures of motor activity, but there was a significant decrease in paw withdrawal threshold in the hind paws at day 14 post-SCI. These findings suggest that an increased release of glutamate in VPL plays a role in secondary pathologic changes, leading to neuronal hyperexcitation and neuropathic pain after SCI.

3,4-Methylenedioxymethamphetamine (MDMA) is known to enhance tactile sensory perception, an effect that contributes to its popularity as a recreational drug. The neurophysiological basis for the effects of MDMA on somatosensation are unknown. However, MDMA interactions with the serotonin transporter (SERT) and subsequent enhancement of serotonin neurotransmission are well known. The rat trigeminal somatosensory system receives serotonergic afferents from the dorsal raphe nucleus. Because these fibers express SERT, they should be vulnerable to MDMA-induced effects. We found that administration of a challenge injection of MDMA (3 mg/kg i.p.) after repeated MDMA treatment (3 mg/kg per day for 4 days) elicits both serotonin and norepinephrine efflux in the ventral posterior medial (VPM) thalamus of Long-Evans hooded rats, the main relay along the lemniscal portion of the rodent trigeminal somatosensory pathway. We evaluated the potential for repeated MDMA administration to modulate whisker-evoked discharge of individual neurons in this region. After surgically implanting stainless steel eight-wire multichannel electrode bundles, we recorded spike train activity of single cells while activating the whisker pathway using a piezoelectric mechanical stimulator. We found that repeated MDMA administration increased the spontaneous firing rate but reduced both the magnitude and duration of whisker-evoked discharge in individual VPM thalamic neurons. The time course of drug action on neuronal firing patterns was generally consistent with fluctuations in neurotransmitter efflux as shown from our microdialysis studies. On the basis of these results, we propose that single use and repeated administration of MDMA may "distort," rather than enhance, tactile experiences in humans, in part, by disrupting normal spike firing patterns through somatosensory thalamic relay circuits.

Chemokines are implicated in the neuroinflammation of several chronic neurodegenerative disorders. However, the precise role of chemokines in neurodegeneration is unknown. Thiamine deficiency (TD) causes abnormal oxidative metabolism in the brain as well as a well-defined microglia activation and neurodegeneration in the submedial thalamus nucleus (SmTN), which are common features of neurodegenerative diseases. We evaluated the role of chemokines in neurodegeneration and the underlying mechanism in a TD model. Among the chemokines examined, TD selectively induced neuronal expression of monocyte chemoattractant protein-1 (MCP-1) in the SmTN prior to microglia activation and neurodegeneration. The conditioned medium collected from TD-induced neurons caused microglia activation. With a neuron/microglia co-culture system, we showed that MCP-1-induced neurotoxicity required the presence of microglia, and exogenous MCP-1 was able to activate microglia and stimulated microglia to produce cytokines. A MCP-1 neutralizing antibody inhibited MCP-1-induced microglia activation and neuronal death in culture and in the thalamus. MCP-1 knockout mice were resistant to TD-induced neuronal death in SmTN. TD selectively induced the accumulation of reactive oxygen species in neurons, and antioxidants blocked TD-induced MCP-1 expression. Together, our results indicated an induction of neuronal MCP-1 during mild impairment of oxidative metabolism caused by microglia recruitment/activation, which exacerbated neurodegeneration., (© 2010 The Authors; Brain Pathology © 2010 International Society of Neuropathology.)

VGLUT1 and VGLUT2 have been reported to show complementary distributions in most brain regions and have been assumed to define distinct functional elements. In the present study, we first investigated the expression of VGLUT1 and VGLUT2 in the trigeminal sensory nuclear complex of the rat by dual-fluorescence in situ hybridization. Although VGLUT1 and/or VGLUT2 mRNA signals were detected in all the nuclei, colocalization was found only in the principal sensory trigeminal nucleus (Vp). About 64% of glutamatergic Vp neurons coexpressed VGLUT1 and VGLUT2, and the others expressed either VGLUT1 or VGLUT2, indicating that Vp neurons might be divided into three groups. We then injected retrograde tracer into the thalamic regions, including the posteromedial ventral nucleus (VPM) and posterior nuclei (Po), and observed that the majority of both VGLUT1- and VGLUT2-expressing Vp neurons were retrogradely labeled with the tracer. We further performed anterograde labeling of Vp neurons and observed immunoreactivies for anterograde tracer, VGLUT1, and VGLUT2 in the VPM and Po. Most anterogradely labeled axon terminals showed immunoreactivities for both VGLUT1 and VGLUT2 in the VPM and made asymmetric synapses with dendritic profiles of VPM neurons. On the other hand, in the Po, only a few axon terminals were labeled with anterograde tracer, and they were positive only for VGLUT2. The results indicated that Vp neurons expressing VGLUT1 and VGLUT2 project to the VPM, but not to the Po, although the functional differences of three distinct populations of Vp neurons, VGLUT1-, VGLUT2-, and VGLUT1/VGLUT2-expressing ones, remain unsettled., ((c) 2010 Wiley-Liss, Inc.)

Cholera toxin subunit B (CTB) is a sensitive neuroanatomical tracer that generally transports retrogradely in the nervous system, and has been used extensively in brightfield microscopy. Recently, Alexa Fluor (AF) conjugates of CTB have been made available, which now allows multiple tracing with CTB. In this study, we examined the efficacy of these new AF-CTB conjugates when injected into the brain, and compared the results to our previous experiences using fluorescent 3k dextran amines. To test this, we injected AF 488 and AF 594 CTB into the anterior cingulate cortex and the medial agranular cortex in the rat, and examined the retrograde transport to the lateral posterior nucleus of the thalamus. We found that CTB was very viscous but yet very sensitive: small injection sites revealed very intense and detailed retrograde labeling. Anterograde transport was seen only when tissue at the injection site was damaged. These findings suggest that AF-CTB is a very reliable and sensitive retrograde tracer, and should be the first choice retrograde tracer for experiments examining multiple pathways within the same brain.

Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct inhibitory input systems have not been systematically characterized in the thalamus. Here, we contrasted the properties of two independent GABAergic pathways in the posterior thalamic nucleus of rat, one input from the reticular thalamic nucleus (nRT), and one "extrareticular" input from the anterior pretectal nucleus (APT). The vast majority of nRT-thalamic terminals formed single synapses per postsynaptic target and innervated thin distal dendrites of relay cells. In contrast, single APT-thalamic terminals formed synaptic contacts exclusively via multiple, closely spaced synapses on thick relay cell dendrites. Quantal analysis demonstrated that the two inputs displayed comparable quantal amplitudes, release probabilities, and multiple release sites. The morphological and physiological data together indicated multiple, single-site contacts for nRT and multisite contacts for APT axons. The contrasting synaptic arrangements of the two pathways were paralleled by different short-term plasticities. The multisite APT-thalamic pathway showed larger charge transfer during 50-100 Hz stimulation compared with the nRT pathway and a greater persistent inhibition accruing during stimulation trains. Our results demonstrate that the two inhibitory systems are morpho-functionally distinct and suggest and that multisite GABAergic terminals are tailored for maintained synaptic inhibition even at high presynaptic firing rates. These data explain the efficacy of extrareticular inhibition in timing relay cell activity in sensory and motor thalamic nuclei. Finally, based on the classic nomenclature and the difference between reticular and extrareticular terminals, we define a novel, multisite GABAergic terminal type (F3) in the thalamus.

Changes in the mRNA expression of neurotransmitters receptors under chronic pain conditions have been described in various areas of the central nervous system (CNS). Delta opioid receptors (DORs) have been implicated in pain mechanisms but, although its mRNA expression has been studied in the rat CNS, there are no reports describing its distribution in specific thalamic and brainstem nuclei during chronic inflammatory pain. Here, in situ hybridization for DOR mRNA was performed in brain sections from control and monoarthritic (MA) rats with 2, 4, 7 and 14 days of inflammation. Grain densities were determined bilaterally in the ventrobasal complex (VB), posterior (Po), centromedial/centrolateral (CM/CL) and reticular (Rt) nuclei of the thalamus, and in the dorsal reticular (DRt), lateral reticular (LRt) and parvocellular reticular (PCRt) nuclei of the brainstem. Control animals exhibited weak mRNA expression in the VB, Po and CM/CL, as well as in PCRt, while moderate grain densities were observed in the Rt, DRt and LRt. During MA, DOR mRNA expression was significantly decreased (22%) in the Rt contralateral to the affected joint at both 7 and 14 days of inflammation, as compared to controls. A bilateral reduction (35%) was also observed in the DRt at 14 days of MA, while a contralateral increase was found in the PCRt at 7 days (+39%). No significant changes were observed in the other regions analyzed. Thus, data show changes in the DOR mRNA expression during the development of chronic inflammatory pain, in thalamic and brainstem nuclei implicated in pain processing mechanisms.

Abnormalities in oxidative metabolism and reductions of thiamine-dependent enzymes accompany many age-related neurodegenerative diseases. Thiamine deficiency (TD) produces a cascade of events including mild impairment of oxidative metabolism, activation of microglia, astrocytes and endothelial cells that leads to neuronal loss in select brain regions. The earliest changes occur in a small, well-defined brain region, the submedial thalamic nucleus (SmTN). In the present study, a micropunch technique was used to evaluate quantitatively the selective regional changes in mRNA and protein levels. To test whether this method can distinguish between changes in vulnerable and non-vulnerable regions, markers for neuronal loss (NeuN) and endothelial cells (eNOS) and inflammation (IL-1beta, IL-6 and TNF-alpha) in SmTN and cortex of control and TD mice were assessed. TD significantly reduced NeuN and increased CD11b, GFAP and ICAM-1 immunoreactivity in SmTN as revealed by immunocytochemistry. When assessed on samples obtained by the micropunch method, NeuN protein declined (-49%), while increased mRNA levels were observed for eNOS (3.7-fold), IL-1beta (43-fold), IL-6 (44-fold) and TNF-alpha (64-fold) in SmTN with TD. The only TD-induced change that occurred in cortex with TD was an increase in TNF-alpha (22-fold) mRNA levels. Immunocytochemical analysis revealed that IL-1beta, IL-6 and TNF-alpha protein levels increased in TD brains and colocalized with glial markers. The consistency of these quantitative results with immunocytochemical measurements validates the micropunch technique. The results demonstrate that TD induces quantitative, distinct inflammatory responses and oxidative stress in vulnerable and non-vulnerable regions that may underlie selective vulnerability.

Connections of representations of the teeth and tongue in primary somatosensory cortex (area 3b) and adjoining cortex were revealed in owl, squirrel, and marmoset monkeys with injections of fluorescent tracers. Injection sites were identified by microelectrode recordings from neurons responsive to touch on the teeth or tongue. Patterns of cortical label were related to myeloarchitecture in sections cut parallel to the surface of flattened cortex, and to coronal sections of the thalamus processed for cytochrome oxidase (CO). Cortical sections revealed a caudorostral series of myelin dense ovals (O1-O4) in area 3b that represent the periodontal receptors of the contralateral teeth, the contralateral tongue, the ipsilateral teeth, and the ipsilateral tongue. The ventroposterior medial subnucleus, VPM, and the ventroposterior medial parvicellular nucleus for taste, VPMpc, were identified in the thalamic sections. Injections placed in the O1 oval representing teeth labeled neurons in VPM, while injections in O2 representing the tongue labeled neurons in both VPMpc and VPM. These injections also labeled adjacent part of areas 3a and 1, and locations in the lateral sulcus and frontal lobe. Callosally, connections of the ovals were most dense with corresponding ovals. Injections in the area 1 representation of the tongue labeled neurons in VPMpc and VPM, and ipsilateral area 3b ovals, area 3a, opercular cortex, and cortex in the lateral sulcus. Contralaterally, labeled neurons were mostly in area 1. The results implicate portions of areas 3b, 3a, and 1 in the processing of tactile information from the teeth and tongue, and possibly taste information from the tongue.

Many studies have implicated GABA(B) receptors in pain transmission mechanisms, especially in the spinal cord. In the thalamus, mRNA expression of the GABA(B(1b)) isoform was shown to be regulated in relay nuclei in response to chronic noxious input arising from experimental monoarthritis. GABA(B(1a)) and GABA(B2) mRNA expression was here determined by in situ hybridisation in the brain of control, 2, 4, 7 and 14 days monoarthritic rats, to evaluate whether this expression was regulated by chronic noxious input in thalamic nuclei. mRNA labelling was analysed quantitatively in the ventrobasal complex, posterior, central medial/central lateral and reticular thalamic nuclei; the thalamic visual relay and dentate gyrus were examined for control. No mRNA expression was detected for GABA(B(1a)) in control and monoarthritic animals. Similarly, GABA(B2) mRNA was not found in the reticular nucleus. However, GABA(B2) mRNA expression was observed in the ventrobasal complex, posterior and central medial/central lateral nuclei of control animals. A significant decrease of 42% at 2 days and 27% at 4 days of monoarthritis was observed in the ventrobasal complex contralaterally, when compared with controls, returning to basal levels at 7 days of monoarthritis. In the ipsilateral posterior nucleus, there was a significant decrease of 38% at 2 days of monoarthritis. No significant changes were observed in central medial/central lateral nuclei. The data suggest that GABA(B2) mRNA expression in the ventrobasal complex and posterior nucleus is regulated by noxious input and that GABA(B) receptors might play a role in the plasticity of these relay nuclei during chronic inflammatory pain.

An unknown chicken gene selected from a published substractive hybridization screen (GenBank Accession No. ; [Christiansen, J.H., Coles, E.G., Robinson, V., Pasini, A., Wilkinson, D.G., 2001. Screening from a subtracted embryonic chick hindbrain cDNA library: identification of genes expressed during hindbrain, midbrain and cranial neural crest development. Mech. Dev. 102, 119-133.]) was deemed of interest because of its dynamic pattern of expression across the forebrain and midbrain regions. A 528bp fragment cloned from early chick embryo cDNA and used for in situ hybridization corresponded to part of the 3' untranslated region of the chicken gene Leucine-rich repeat neuronal protein 1 (Lrrn1). The expression of this gene, mapped in the embryonic chick brain between stages HH10 and HH26, apparently preconfigures the zona limitans thalami site before overt formation of this boundary structure. Apart of colateral expression in the forebrain, midbrain and hindbrain basal plate, the most significant expression of Lrrn1 was found early on across the entire alar plate of midbrain and forebrain (HH10). This unitary domain soon divides at HH14 into a rostral part, across alar secondary prosencephalon and prospective alar prosomere 3 (prethalamus; caudal limit at the prospective zona limitans), and a caudal part in alar prosomere 1 (pretectum) and midbrain. The rostral forebrain domain later downregulates gradually most extratelencephalic signal of Lrrn1, but the rostral shell of zona limitans retains expression longer. Expression in the caudal alar domain also changes by downregulation within its pretectal subdomain. Caudally, the midbrain domain ends at the isthmo-mesencephalic junction throughout the studied period. Embryonic Lrrn1 signal also appears in the somites and in the otic vesicle.

An adenovirus vector was generated using a neuron-specific promoter synapsin I and enhanced green fluorescent protein (EGFP) reporter (AdSynEGFP). In addition, two modifications were identified that resulted in robust and reliable retrograde transport and EGFP expression after injection of the virus into three different brain regions in adult rats (medial prefrontal cortex, posterior thalamic nuclear group, and CA1). These are postinjection survival times of 14 days and addition of high concentrations of NaCl (>or=600 mM) to the injection buffer. These modifications resulted in obvious improvement in the intensity of the EGFP signal and in the number of labeled cells. Use of anti-EGFP in immunofluorescence or immunoperoxidase processing further enhanced the signal so that Golgi-like filling of dendritic spines and axon collaterals was routinely achieved. Effectiveness of the AdSynEGFP for Golgi-like filling was confirmed in one rhesus monkey with injections in visual area V4. Because of the long-term viability of the infected neurons (at least up to 28 days in rats and 22 days in monkey), this AdSynEGFP is suitable for use in microcircuitry studies in combination with other fluorescently tagged elements, including anterogradely labeled extrinsic projections. The native EGFP signal (without antibody enhancement) may be sufficient for studies involving cultured cells or slices.

Striatal projections from the lateral intermediate (LI) and posterior (Po) thalamic complexes were studied with the anterograde tracers wheat germ agglutinin-horseradish peroxidase and Phaseolus vulgaris leucoagglutinin. Projections to the lateral part of the head and body of the caudate nucleus (CN) and to the putamen (Pu) were found to arise from the ventral parts of the caudal subdivision of the LI besides the well established sources in the intralaminar and ventral thalamic nuclei. No projections to the CN and only a few to the Pu were found to arise from the medial division of the Po. The presence of terminal and intercalated varicosities in the thalamostriatal fibers suggests that they form both terminal and en passant synapses. Thalamostriatal fibers from these thalamic sectors were unevenly distributed within the CN, with patches of either low-density innervation or with no projections at all interspersed within irregular, more densely innervated areas. The former coincided with the acetylcholinesterase-poor striosomes and the latter areas of dense projection with the extrastriosomal matrix.

Neurons containing tuberoinfundibular peptide of 39 residues (TIP39) constitute a rostro-caudally elongated group of cells in the posterior thalamus. These neurons are located in the rostral part of the subparafascicular nucleus and in the subparafascicular area, caudally. Projections of the caudally located TIP39 neurons have been previously identified by their disappearance following lesions. We have now mapped the projections of the rat rostral subparafascicular neurons using injections of the anterograde tracer biotinylated dextran amine and the retrograde tracer cholera toxin B subunit, and confirmed the projections from more caudal areas previously inferred from lesion studies. Neurons from both the rostral subparafascicular nucleus and the subparafascicular area project to the medial prefrontal, insular, ecto- and perirhinal cortex, nucleus of the diagonal band, septum, central and basomedial amygdaloid nuclei, fundus striati, basal forebrain, midline and intralaminar thalamic nuclei, hypothalamus, subthalamus and the periaqueductal gray. The subparafascicular area projects more densely to the amygdala and the hypothalamus. In contrast, only the rostral part of the subparafascicular nucleus projects significantly to the superficial layers of prefrontal, insular, ectorhinal and somatosensory cortical areas. Double labeling showed that anterogradely labeled fibers from the rostral part of the subparafascicular nucleus contain TIP39 in many forebrain areas, but do not in hypothalamic areas. Injections of the retrograde tracer cholera toxin B subunit into the lateral septum and the fundus striati confirmed that they were indeed target regions of both the rostral subparafascicular nucleus and the subparafascicular area. In contrast, TIP39 neurons did not project to the anterior hypothalamic nucleus. Our data provide an anatomical basis for the potential involvement of rostral subparafascicular neurons in limbic and autonomic regulation, with TIP39 cells being major subparafascicular output neurons projecting to forebrain regions.

Our previous studies have indicated that the thalamic nucleus submedius (Sm) is involved in modulation of nociception and plays an important role in an endogenous analgesic system (a feedback loop) consisting of spinal cord-Sm-ventrolateral orbital cortex-periaqueductal gray-spinal cord. To investigate whether opioids are involved in this antinociception pathway, the effects of microinjection of morphine and naloxone into the Sm on the nociceptive behavior (agitation) evoked in the formalin test were investigated in the awake rat using an automated movement detection system. The results indicate that a unilateral microinjection of morphine (5 micro g, 0.5 microl) into the Sm suppresses the formalin-induced agitation response, but does not influence spontaneous motor activity, and that the morphine-induced depression can be reversed by microinjection of the opioid receptor antagonist naloxone (1.0 micro g, 0.5 microl) into the same Sm site. The results suggest that opioid receptors in the Sm may be involved in the Sm-mediated depression of persistent inflammatory pain.

Corticotropin-releasing hormone (CRH) coordinates multiple aspects of the stress response. Recently, CRH mRNA has been identified in two regions of the thalamus: the posterior nuclear group (Po), and a region located at the interface of the central medial and ventral posteromedial nucleus (parvicellular part) (CM-VPMpc). Previous studies demonstrated that in both regions CRH mRNA increases following 1 h of restraint stress, suggesting involvement of thalamic CRH in processing somatosensory and visceral information related to stress. The current study was proposed to further understand the effects of repeated and acute restraint stress on levels of thalamic CRH mRNA. Adult male rats were assigned to one of four groups in a 2 (repeated stress, no repeated) x2 (acute, no acute) design. Brain sections were processed for CRH mRNA in situ hybridization. ANOVA revealed no main effects of acute or repeated stress in either thalamic region. However, significant interactions between acute and repeated stress for levels of CRH mRNA were found for both regions of the thalamus. Compared to the no stress condition, acute restraint significantly increased CRH mRNA in the Po (39%) and the CM-VPMpc (32%). Repeated restraint did not alter baseline CRH mRNA levels, but blocked the acute restraint-induced effects. Thus, while acute stress increases levels of thalamic CRH mRNA, repeated exposure to the same stressor is without effect and prevents the acute response. These findings add to data establishing a role for thalamic CRH in the stress response and suggest a mechanism that may underlie habituation to repeated stress exposure.