POm Thalamocortical Input Drives Layer-Specific Microcircuits in Somatosensory Cortex.

Higher-order thalamic nuclei, such as the posterior medial nucleus (POm) in the somatosensory system or the pulvinar in the visual system, densely innervate the cortex and can influence perception and plasticity. To systematically evaluate how higher-order thalamic nuclei can drive cortical circuits, we investigated cell-type selective responses to POm stimulation in mouse primary somatosensory (barrel) cortex, using genetically targeted whole-cell recordings in acute brain slices. We find that ChR2-evoked thalamic input selectively targets specific cell types in the neocortex, revealing layer-specific modules for the summation and processing of POm input. Evoked activity in pyramidal neurons from deep layers is fast and synchronized by rapid feedforward inhibition from GABAergic parvalbumin-expressing neurons, and activity in superficial layers is weaker and prolonged, facilitated by slow inhibition from GABAergic neurons expressing the 5HT3a receptor. Somatostatin-expressing GABAergic neurons do not receive direct input in either layer and their spontaneous activity is suppressed during POm stimulation. This novel pattern of weak, delayed, thalamus-evoked inhibition in layer 2 suggests a longer integration window for incoming sensory information and may facilitate stimulus detection and plasticity in superficial pyramidal neurons.

Specification of neurotransmitter identity by Tal1 in thalamic nuclei.

BACKGROUND: The neurons contributing to thalamic nuclei are derived from at least two distinct progenitor domains: the caudal (cTH) and rostral (rTH) populations of thalamic progenitors. These neural compartments exhibit unique neurogenic patterns, and the molecular mechanisms underlying the acquisition of neurotransmitter identity remain largely unclear. RESULTS: T-cell acute lymphocytic leukemia protein 1 (Tal1) was expressed in the early postmitotic cells in the rTH domain, and its expression was maintained in mature thalamic neurons in the ventrolateral geniculate nucleus (vLG) and the intergeniculate leaflet (IGL). To investigate a role of Tal1 in thalamic development, we used a newly generated mouse line driving Cre-mediated recombination in the rTH domain. Conditional deletion of Tal1 did not alter regional patterning in the developing diencephalon. However, in the absence of Tal1, rTH-derived thalamic neurons failed to maintain their postmitotic neuronal features, including neurotransmitter profile. Tal1-deficient thalamic neurons lost their GABAergic markers such as Gad1, Npy, and Penk in IGL/vLG. These defects may be associated at least in part with down-regulation of Nkx2.2, which is known as a critical regulator of rTH-derived GABAergic neurons. CONCLUSIONS: Our results demonstrate that Tal1 plays an essential role in regulating neurotransmitter phenotype in the developing thalamic nuclei. Developmental Dynamics 246:749-758, 2017. © 2017 Wiley Periodicals, Inc.

REM sleep deprivation induces changes of down regulatory antagonist modulator (DREAM) expression in the ventrobasal thalamic nuclei of sprague-dawley rats.

REM sleep is a crucial component of sleep. Animal studies indicate that rapid eye movement (REM) sleep deprivation elicits changes in gene expression. Down regulatory antagonist modulator (DREAM) is a protein which downregulates other gene transcriptions by binding to the downstream response element site. The aim of this study is to examine the effect of REM sleep deprivation on DREAM expression in ventrobasal thalamic nuclei (VB) of rats. Seventy-two male Sprague-Dawley rats were divided into four major groups consisting of free-moving control rats (FMC) (n = 18), 72-h REM sleep-deprived rats (REMsd) (n = 18), 72-h REM sleep-deprived rats with 72-h sleep recovery (RG) (n = 18), and tank control rats (TC) (n = 18). REM sleep deprivation was elicited using the inverted flower pot technique. DREAM expression was examined in VB by immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) studies. The DREAM-positive neuronal cells (DPN) were decreased bilaterally in the VB of rats deprived of REM sleep as well as after sleep recovery. The nuclear DREAM extractions were increased bilaterally in animals deprived of REM sleep. The DREAM messenger RNA (mRNA) levels were decreased after sleep recovery. The results demonstrated a link between DREAM expression and REM sleep deprivation as well as sleep recovery which may indicate potential involvement of DREAM in REM sleep-induced changes in gene expression, specifically in nociceptive processing.

Developmental GnRH signaling is not required for sexual differentiation of kisspeptin neurons but is needed for maximal Kiss1 gene expression in adult females.

Kisspeptin, encoded by Kiss1, stimulates reproduction. In rodents, one Kiss1 population resides in the hypothalamic anterior ventral periventricular nucleus and neighboring rostral periventricular nucleus (AVPV/PeN). AVPV/PeN Kiss1 neurons are sexually dimorphic (greater in females), yet the mechanisms regulating their development and sexual differentiation remain poorly understood. Neonatal estradiol (E2) normally defeminizes AVPV/PeN kisspeptin neurons, but emerging evidence suggests that developmental E2 may also influence feminization of kisspeptin, although exactly when in development this process occurs is unknown. In addition, the obligatory role of GnRH signaling in governing sexual differentiation of Kiss1 or other sexually dimorphic traits remains untested. Here, we assessed whether AVPV/PeN Kiss1 expression is permanently impaired in adult hpg (no GnRH or E2) or C57BL6 mice under different E2 removal or replacement paradigms. We determined that 1) despite lacking GnRH signaling in development, marked sexual differentiation of Kiss1 still occurs in hpg mice; 2) adult hpg females, who lack lifetime GnRH and E2 exposure, have reduced AVPV/PeN Kiss1 expression compared to wild-type females, even after chronic adulthood E2 treatment; 3) E2 exposure to hpg females during the pubertal period does not rescue their submaximal adult Kiss1 levels; and 4) in C57BL6 females, removal of ovarian E2 before the pubertal or juvenile periods does not impair feminization and maximal adult AVPV/PeN Kiss1 expression nor the ability to generate LH surges, indicating that puberty is not a critical period for Kiss1 development. Thus, sexual differentiation still occurs without GnRH, but GnRH or downstream E2 signaling is needed sometime before juvenile development for complete feminization and maximal Kiss1 expression in adult females.

IL-1ß is induced in reactive astrocytes in the somatosensory cortex of rats with genetic absence epilepsy at the onset of spike-and-wave discharges, and contributes to their occurrence.

Interleukin (IL)-1ß plays a crucial role in the mechanisms of limbic seizures in rodent models of temporal lobe epilepsy. We addressed whether activation of the IL-1ß signaling occurs in rats with genetic absence epilepsy (GAERS) during the development of spike-and-wave discharges (SWDs). Moreover, we studied whether inhibition of IL-1ß biosynthesis in GAERS could affect SWD activity. IL-1ß expression and glia activation were studied by immunocytochemistry in the forebrain of GAERS at postnatal days (PN)14, PN20, and PN90 and in age-matched non-epileptic control Wistar rats. In PN14 GAERS, when no SWDs have developed yet, IL-1ß immunostaining was undetectable, and astrocytes and microglia showed a resting phenotype similar to control Wistar rats. In 3 out of 9 PN20 GAERS, IL-1ß was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence of immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1ß was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions. An age-dependent c-fos activation was found in the somatosensory cortex of GAERS with maximal levels reached in PN90 rats; c-fos was also induced in some thalamic nuclei in PN20 and PN90 GAERS. Inhibition of IL-1ß biosynthesis in PN90 GAERS by 4-day systemic administration of a specific ICE/Caspase-1 blocker, significantly reduced both SWD number and duration. These results show that IL-1ß is induced in reactive astrocytes of the somatosensory cortex of GAERS at the onset of SWDs. IL-1ß has pro-ictogenic properties in this model, and thus it may play a contributing role in the mechanisms underlying the occurrence of absence seizures.

A computational model of thalamocortical dysrhythmia.

Functional stereotactic lesions in the central lateral nucleus of the medial thalamus have proved to be an effective treatment of neurogenic pain and other neurological disorders associated with thalamocortical dysrhythmia. The mechanisms underlying patient recovery after surgery are currently being explored using quantitative electroencephalography. Here we test the hypothesis that the particular role played by the non-specific medial thalamic nuclei in thalamocortical dysrhythmia is based on the divergent connectivity between these non-specific and reticular nuclei. We built a spiking computer model of the human thalamocortical system consisting of specific, non-specific and reticular thalamic nuclei. In our simulations of the thalamocortical system, deafferentation of peripheral thalamic afferents leads to hyperpolarization and subsequent bursting in the reticular nucleus. This provides strong inhibitory feedback to both the specific and the non-specific thalamic nuclei and initiates a feedback cycle of thalamic bursts in the theta frequency range. The divergent connections between the reticular and non-specific thalamic nuclei provide synchronization of the oscillating circuits. Functional silencing of the non-specific model nucleus limits reverberation and rescues the system from these oscillations. The same effect could be achieved by increasing the input to the non-specific nucleus from cortical areas. The model predicts that the invasiveness of functional neurosurgery can be reduced by targeting only deafferented areas in the medial nuclei as these are the key areas for generation and maintenance of pathological rhythms.

Cell type-specific thalamic innervation in a column of rat vibrissal cortex.

This is the concluding article in a series of 3 studies that investigate the anatomical determinants of thalamocortical (TC) input to excitatory neurons in a cortical column of rat primary somatosensory cortex (S1). We used viral synaptophysin-enhanced green fluorescent protein expression in thalamic neurons and reconstructions of biocytin-labeled cortical neurons in TC slices to quantify the number and distribution of boutons from the ventral posterior medial (VPM) and posteromedial (POm) nuclei potentially innervating dendritic arbors of excitatory neurons located in layers (L)2-6 of a cortical column in rat somatosensory cortex. We found that 1) all types of excitatory neurons potentially receive substantial TC input (90-580 boutons per neuron); 2) pyramidal neurons in L3-L6 receive dual TC input from both VPM and POm that is potentially of equal magnitude for thick-tufted L5 pyramidal neurons (ca. 300 boutons each from VPM and POm); 3) L3, L4, and L5 pyramidal neurons have multiple (2-4) subcellular TC innervation domains that match the dendritic compartments of pyramidal cells; and 4) a subtype of thick-tufted L5 pyramidal neurons has an additional VPM innervation domain in L4. The multiple subcellular TC innervation domains of L5 pyramidal neurons may partly explain their specific action potential patterns observed in vivo. We conclude that the substantial potential TC innervation of all excitatory neuron types in a cortical column constitutes an anatomical basis for the initial near-simultaneous representation of a sensory stimulus in different neuron types.

Pattern of distribution of serotonergic fibers to the thalamus of the rat.

It is well established that serotonergic (5-hydroxytryptamine, 5-HT) fibers, mainly originating from the dorsal and median raphe nuclei of the brainstem, distribute throughout the forebrain, most heavily to 'limbic' forebrain structures. Few reports have examined the distribution of 5-HT fibers to the thalamus and none to our knowledge using immunoprocedures for the detection of the serotonin transporter (SERT)-a very sensitive marker for 5-HT fibers. Using immunohistochemical methods for SERT, we examined the pattern of distribution of 5-HT fibers to the thalamus in the rat. We show that serotonergic fibers are heavily concentrated in midline, intralaminar and association nuclei of the thalamus, and with the exception of the lateral geniculate complex, weakly distributed to principal nuclei of thalamus. Specifically, we demonstrate that 5-HT fibers are densely concentrated in the anteroventral, anteromedial and interanteromedial nuclei of the anterior thalamus, the paraventricular, rhomboid and reuniens nuclei of the midline thalamus, the central medial and central lateral nuclei of the intralaminar thalamus, the intermediodorsal nucleus, the lateral dorsal nucleus, and the dorsal and ventral lateral geniculate nuclei and intergeniculate leaflet of the LGN complex. Less densely innervated sites include the mediodorsal, paracentral, parafascicular, lateral posterior and submedial nuclei of thalamus. Remaining regions of the thalamus, largely consisting of principal nuclei, contained few 5-HT fibers. This pattern of 5-HT innervation indicates that serotonin/ serotonergic fibers mainly affect thalamic nuclei with connections to 'non-principal' or limbic regions of the cortex (or forebrain). This suggests that serotonergic fibers to the thalamus may exert a significant influence on affective and cognitive functions, possibly complementing the actions of 5-HT fibers to other parts of the brain involved in emotional and cognitive behaviors.

Maturation of kisspeptinergic neurons coincides with puberty onset in male rats.

Kisspeptins, derived from the Kiss1 gene play a central role in activation of the hypothalamo-pituitary gonadal (HPG) axis via stimulation of GnRH neurons. Both Kiss1 and Kiss1R (receptor) mRNA levels are found to be low in pre-pubertal rats, but whether an increase in kisspeptin and/or its receptor is the primary component in the initiation of puberty and where in the hypothalamus regulation of the kisspeptin/Kiss1R system occurs is unresolved. Using immunohistochemistry and in situ hybridization, we analyzed the level of Kiss1 mRNA and kisspeptin-immunoreactivity in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus of male rats along pubertal development. Neurons expressing Kiss1 mRNA were first detected at PND15, but increased significantly around puberty, and declined again in the adult rat. While virtually no immunoreactive cell bodies were detectable in the AVPV at any age, numerous kisspeptin-positive neurons in the arcuate nucleus were detected in the adult rat. Increasing doses of kisspeptin-54 given peripherally to male rats at PND15, 30, 45, and 60 evoked roughly similar effects, as revealed by the induction of c-Fos in the pituitary and secretion of LH and testosterone. These results show that both Kiss1 mRNA and the peptide increase in arcuate nucleus along pubertal maturation. Since kisspeptin signaling is potentially functional, even for peripheral activation, and well before the kisspeptin neuronal system is fully matured, our data support that the regulation of kisspeptin synthesis and release are key events in puberty onset in the male rat.

Characterization of parabrachial subnuclei in mice with regard to salt tastants: possible independence of taste relay from visceral processing.

We examined whether salt taste and/or abdominal illness were dealt within different subnuclei in the parabrachial nucleus (PBN) in mice, using retrograde tracing methods and c-Fos-like immunoreactivity (FLI) detection procedures. Some PBN subnuclei have distinct functions and receive various sensory inputs from the nucleus of the solitary tract (NTS) and other areas and relay them to the higher order nuclei such as the thalamus. The afferent-dependent pattern of FLI has been investigated in the PBN. However, it is unclear in which PBN subnuclei the tastants induce c-Fos, or whether PBN subnuclei process taste inputs separately from other inputs, or integrate them. After the tracer injections into the thalamic taste relay, the retrograde labeled cells revealed the taste relay cells in the PBN at the boundary with the superior cerebellar peduncle of both the inner part of the external lateral subnucleus and the medial subnucleus and in the waist area. On the other hand, NaCl intake induced intense FLI in the dorsal lateral subnucleus, whereas LiCl intake yielded intense FLI in both the dorsal lateral subnucleus and the outer part of the external lateral subnucleus. Thus, the present findings that subnuclei relaying taste information to the thalamus do not yield FLI in response to salt taste and abdominal illness indicate that they lack FLI yielding pathways or that they are independent from the subnuclei processing salt taste and visceral information via c-Fos in mice.

Neurogenic development of the auditory areas of the midbrain and diencephalon in the Xenopus laevis and evolutionary implications.

To study whether the core-versus-shell pattern of neurogenesis occurred in the mesencephalic and diencephalic auditory areas of amniotes also appears in the amphibian, [(3)H]-thymidine was injected into tadpoles at serial developmental stages of Xenopus laevis. Towards the end of metamorphism, [(3)H]-thymidine labeling was examined and led to two main observations: 1) neuron generation in the principal nucleus (Tp) started at stage 50, and peaked at stage 53, whereas it began at stage 48.5, and peaked around stage 49 in the other two mesencephalic auditory areas, the laminar nucleus (Tl) and the magnocellular nucleus (Tmc). 2) Neuron generation appeared at stage 40, and peaked around stage 52 in the posterior thalamic nucleus (P) and the central thalamic nucleus (C). Our study revealed that, like the cores of mesencephalic auditory nuclei in amniotes, Tp showed differences from Tl and Tmc in the onset and the peak of neurogenesis. However, such differences did not occur in the P and C. Our neurogenetic data were consistent with anatomical and physiological reports indicating a clear distinction between the mesencephalic, but not the diencephalic auditory areas of the amphibian. Our data are helpful to get insights into the organization of auditory nuclei and its evolution in vertebrates.

The trajectory of sensory pathways from the lamina terminalis to the insular and cingulate cortex: a neuroanatomical framework for the generation of thirst.

The pathways involved in the emotional aspects of thirst, the arousal and affect associated with the generation of thirst and the motivation to obtain satiation, have been studied but remain poorly understood. Rats were therefore injected with the neurotropic virus pseudorabies in either the insular or cingulate cortex. After 2 days of infection, pseudorabies-positive neurons were identified within the thalamus and lamina terminalis. In a separate group of rats, the retrograde tracer cholera toxin subunit b (CTb) was used in combination with either isotonic (0.15 M NaCl) or hypertonic (0.8 M NaCl) saline (1 ml/100 g body wt ip). Rats injected with CTb in the insular cortex and stimulated with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the paraventricular, rhomboid, and reuniens thalamic nuclei, whereas those rats injected with CTb in the cingulate cortex and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the medial part of the mediodorsal, interanteromedial, anteromedial, and ventrolateral part of the laterodorsal thalamic nuclei. Rats injected with CTb in the dorsal midline of the thalamus and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons within the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and insular cortex but not the subfornical organ. A small proportion of the CTb-positive neurons in the OVLT were immunopositive for transient receptor potential vanilloid 1, a putative osmoresponsive membrane protein. These results identify functional thalamocortical pathways involved in relaying osmotic signals to the insular and cingulate cortex and may provide a neuroanatomical framework for the emotional aspects of thirst.

Differential activation of anterior and midline thalamic nuclei following retrieval of aversively motivated learning tasks.

Two thalamic nuclear groups, the anterior thalamic nuclei (ATN) and midline and intralaminar thalamic complex (MITC) have connections to the prefrontal cortex, amygdala, hippocampus and accumbens that are important for learning and memory. However, the anatomical proximity between the ATN and MITC makes it difficult to reveal their roles in memory retrieval of aversive conditioned behavior. To address the issue, we explored the activation of the ATN and MITC, as represented by the expression of the immediate early gene c-fos, following either the retrieval of a conditioned taste aversion (CTA) induced by taste-LiCl pairing (visceral aversion) or of inhibitory avoidance (IA) induced by context-foot shock pairing (somatic aversion) in rats. The anterodorsal (AD) nucleus in the ATN was activated by foot shock and the recall of IA, but not by i.p. injection of LiCl or the recall of CTA. No significant elevation was observed in the other ATN following these treatments. Among nuclei of the MITC, the paraventricular thalamic nucleus (PVT) was activated by the delivery of shock or LiCl and by the recall of both CTA and IA, while the mediodorsal thalamus (MD) and central medial and intermediate thalamus (CM/IMD) were not. The innately aversive taste of quinine did not elevate c-fos expression in either the ATN or MITC. These results suggest that the PVT in the MITC is involved in the processing and retrieval of both taste-malaise and context-shock association tasks, while the AD in the ATN is involved in those of context-shock association only. The difference of the activity between the ATN and MITC demonstrates their functional and anatomical heterogeneity in neural substrates for aversive learning tasks.

Mast cells accumulate in the anogenital region of somatosensory thalamic nuclei during estrus in female mice.

Mast cells are located in the mammalian thalamus where their numbers are sensitive to reproductive hormones. To evaluate whether differences between sexes and over the estrus cycle influence the nuclear distribution of mast cells in mice, we mounted a comprehensive analysis of their distribution in males compared to females and in females over the estrus cycle. Compared to males, mast cells were more numerous in the lateral intralaminar and posterior nuclei of females during estrus and in the ventral posterolateral (VPL) and medial geniculate nuclei during proestrus. During estrus, mast cells were especially concentrated in those regions within the VPL and posterior thalamic nuclei that receive somatosensory information from the anogenital region. Treatment of ovariectomized mice with estrogen increased the number and the percent of mast cells that were degranulated compared to that after ovariectomy alone, an effect that was most apparent in the lateral intralaminar, VPL and posterior nuclei. In estrogen-primed, ovariectomized females, progesterone delivered 5 h before tissue collection counteracted the effects of estrogen. Cromolyn, a mast cell stabilizer, injected centrally 1 h prior to and 24 h after estrogen in ovariectomized mice, prevented the increase in number of mast cells in the whole thalamus and in the intralaminar, VPL and posterior nuclei. This suggests that estrogen induces hyperplasia by a mechanism that involves mast cell degranulation. Based on the discrete anatomical location of mast cells in areas of somatosensory nuclei that receive anogenital input together with the temporal correspondence of these cells with estrus, mast cells are well situated to influence sensory input in females during mating.

Characterization of [125I]ZM 241385 binding to adenosine A2A receptors in the pineal of sheep brain.

Adenosine is a ubiquitous neuromodulator and homeostatic regulator that exerts its physiologic actions through activation of A(1), A(2A), A(2B) and A(3) adenosine receptor subtypes. In the central nervous system, adenosine's action in neurons is manifested in its modulation of tonic inhibitory control. Adenosine released in the brain during hypoxia has critical depressant effects on breathing in fetal and newborn mammals, an action suggested to be mediated by A(2A) receptors in the posteromedial thalamus. In an effort to more accurately define the spatial distribution of adenosine A(2A) receptors in fetal sheep diencephalon, we have used a receptor autoradiographic technique utilizing an iodinated radioligand [(125)I]ZM 241385, which has greater sensitivity and resolution than the tritiated compound. The distribution of ligand binding sites in the fetal sheep diencephalon indicated that the highest levels of binding were in select thalamic nuclei, including those implicated in hypoxic depression of fetal breathing, and the pineal. Given the high density of labeled A(2A) receptors in the pineal, these sites were characterized more fully in homogenate radioligand binding assays. These data indicate that [(125)I]ZM 241385 binding sites display a pharmacological signature consistent with that of adenosine A(2A) receptors and are expressed at similar levels in fetal, lamb and adult ovine brain. The adenosine A(2A) receptor pharmacologic signature of the [(125)I]ZM 241385 binding site in pineal cell membranes generalized to the site characterized in membranes derived from other portions of the lamb thalamus, including the sector involved in hypoxic inhibition of fetal breathing. These results have important implications for the functional roles of adenosine A(2A) receptors in the thalamus and pineal of sheep brain.

Post-hypoxic myoclonus induces Fos expression in the reticular thalamic nucleus and neurons in the brainstem.

Post-hypoxic myoclonus is a movement disorder characterized by brief, sudden involuntary muscle jerks. Although the mechanism underlying this disorder remains unclear, earlier pharmacological studies indicated that aberrant activity of specific neuronal circuitry in the central nervous system causes this disorder. In the present study, Fos protein, an immediate-early gene product, was used as a marker of neuronal activity to identify the brain nuclei possibly involved in post-hypoxic myoclonus. We found that Fos protein was immunologically detected in the reticular thalamic nucleus (RT), the medial longitudinal fasciculus (MLF) as well as in the locus coeruleus (LC) and the periventricular gray substance (PVG) in post-hypoxic rats that developed myoclonus in response to auditory stimuli. Fos was not detected in these nuclei from rats that underwent 4 min of cardiac arrest without myoclonus. Electrolytic lesions of the RT or MLF but not the LC/PVG significantly reduced auditory stimulated myoclonus in the post-hypoxic rats. The results suggest that neuronal activity in the RT and the MLF plays a contributing role in post-hypoxic myoclonus.

Pain and temperature encoding in the human thalamic somatic sensory nucleus (Ventral caudal): inhibition-related bursting evoked by somatic stimuli.

Stimulus-evoked inhibitory events have not been demonstrated in thalamic spike trains encoding of pain and temperature stimuli. We have now tested the hypothesis that the human thalamic response to mechanical and thermal stimuli is characterized by low-threshold calcium spike (LTS)-associated bursts of high-frequency action potentials preceded by prolonged inhibition. The results included 57 neurons recorded in the human thalamic principal somatic sensory nucleus (ventral caudal, Vc) of 24 patients during awake surgery. Neurons were classified by the grading of their response with stimulus intensity into the painful range (graded or non-graded) and the stimulus response (to mechanical, cold, or heat stimuli). Firing rates were analyzed by the response to all stimuli combined (stimuli overall) and to the stimulus characteristic of the stimulus response type (optimal stimulus), e.g., cold stimuli for neurons of the cold stimulus response type. All neuronal categories had clear stimulus-evoked LTS bursting as identified by the criteria for selecting bursts in the spike train, by significant preburst inhibition, and by preburst inter-spike interval not significantly <100 ms. Stimulus-evoked LTS burst rates were significantly higher for neurons in the cold stimulus response type independent of the firing rate between bursts. The parameters of preburst inhibition were largely independent of the neuronal category and the stimuli included in the analysis, which suggests inhibitory mechanisms are similar across neuronal types. Therefore LTS bursting is a substantial, nonlinear component of the spontaneous and stimulus-evoked activity of thalamic neurons in awake humans.

A maternal blood-borne factor promotes survival of the developing thalamus.

In this report, we describe the identification of a polypeptide survival-promoting factor that is produced by maternal and early postnatal peripheral blood mononuclear cells (PBMCs) of the immune system in Long-Evans rats and humans. The factor, termed Y-P30, most likely arises from proteolytic processing of a larger precursor protein and accumulates mainly in pyramidal neurons of the developing cortex and hippocampus but not in astrocytes. It was released from neurons grown in culture and substantially promotes survival of cells in explant monocultures of perinatal thalamus from the offspring. Y-P30 mRNA was not detectable in infant or adult brain and was present only in blood cells of pregnant rats and humans but not in nonpregnant controls. However, Y-P30 transcription could be induced in PBMCs of adult animals by a central nervous system lesion (i.e., optic nerve crush), which points to a potential role of the factor not only in neuronal development but also in neuroinflammation after white matter injury.

Induction of c-fos in specific thalamic nuclei following stimulation of the pedunculopontine tegmental nucleus.

The pedunculopontine tegmental nucleus (PPTg) is a major source of cholinergic input to the thalamus. Tracing studies have established that the PPTg has projections to many thalamic nuclei and electrophysiological studies have shown acetylcholine (ACh) to have characteristic effects on thalamic neurons. Behavioural studies point to a role for the PPTg in attention and it is possible that a key substrate for this is the ability of the PPTg to modify sensorimotor gating through the thalamus. However, it is not clear how altered PPTg activity effects neuronal activity across the thalamus en masse. We have attempted to examine this by stimulating the PPTg in freely moving rats and measuring thalamic activation with c-fos immunohistochemistry. The PPTg was stimulated by unilateral microinjection of the L-glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) with the rationale that reuptake blockade increases locally the availability of endogenous neurotransmitter. It was shown that PDC microinjection into PPTg produced clear and consistent changes in Fos immunoreactivity in several thalamic nuclei, but most markedly in the centrolateral, ventrolateral and reticular nuclei. A second study was carried out to determine the gross behavioural effects of intra-PPTg L-glutamate blockade. No changes in locomotion or other general behaviours were observed, indicating that observed changes in thalamic Fos expression were not the result of increased behavioural output but rather a direct consequence of increased neuronal activity from PPTg input. The present data extend previous work establishing pedunculopontine-thalamic connections by specifying which particular nuclei are most affected by PPTg activation.

Distinct patterns of hippocampal formation activity associated with different spatial tasks: a Fos imaging study in rats.

Fos levels were measured in rats trained in one of two qualitatively different spatial memory tasks in a water maze. In one task, ( landmark condition) rats found a submerged platform that was always 25 cm south of a visible landmark, the absolute position of the platform and landmark changing after every trial. In the other task ( place condition), rats swam to a platform that remained in the same absolute position on every session, but changed session to session, with this task relying on the memory of allocentric cues. Despite matched swim times, the landmark condition resulted in higher levels of Fos in a wide range of cortical and subcortical sites, including the hippocampus and its connections. Structural equation modelling revealed two different patterns of hippocampal function. In the allocentric place task there was a significant association between Fos activity in the entorhinal cortices and the hippocampus proper, while in the non-allocentric landmark task this relationship was not present, but was replaced by a connection from the entorhinal cortices to the subiculum. Thus, the two different tasks engage two different modes of hippocampal activity as demonstrated by Fos expression.