Ventrobasal Thalamus Research Articles

Inhibitory effect of 17β-estradiol in the parabrachial nucleus is mediated by GABA

In the present investigation, electrophysiological recordings of thalamic relay neurons were used to investigate the role of estrogen as a modulator of visceral afferent information through the PBN to forebrain structures. Experiments were done in anaesthetized (sodium thiobutabarbitol; 100 mg/kg) male and ovariectomized female rats supplemented for 7 days prior with either 17β-estradiol (OVX-E 2) or saline (OVX-S). A portion of the right cervical vagus was isolated for the electrical activation (0.8 Hz, 2 ms duration) of visceral afferents. The evoked single and multi-unit activity was recorded via a recording electrode in the ventrobasal thalamus. Exogenous microinjection of 17β-estradiol (0.1, 0.25 and 0.5 μM; 200 nl) into the parabrachial nucleus (PBN) produced a significant, dose-dependent attenuation in the magnitude of visceral afferent activation-evoked responses of neurons recorded in the thalamus in both male and OVX-E 2 groups. No effect on evoked thalamic activity was observed following injection of estrogen into the PBN of OVX-S animals. Co-injection of estrogen with the GABA A receptor antagonist, bicuculine (0.1 μM; 200 nl) but not phaclofen (GABA B; 0.1, 0.5 or 1 μM; 200 nl) resulted in an increase in the evoked thalamic response in males (55±11%) and OVX-E 2 female (68±15%) rats. These studies suggest that estrogen inhibits neurotransmission in the PBN via an interaction with the GABA A receptor to modulate the flow of visceral information to the thalamus.

Disruption of Layers 3 and 4 during Development Results in Altered Thalamocortical Projections in Ferret Somatosensory Cortex

The precision of projections from dorsal thalamus to neocortex are key toward understanding overall cortical organization and function. To identify the significance of layer 4 cells in receiving the bulk of thalamic projections in somatosensory cortex, we disrupted layer 4 genesis and studied the effect on thalamic terminations in ferrets. Second, we ascertained the result of layer 4 disruption on functional responses and topographic organization. Methylazoxy methanol (MAM) was injected into pregnant ferrets on embryonic day 33 (E33), when most layer 4 neurons of somatosensory cortex are generated. This treatment resulted in dramatic reduction in the thickness of targeted layer 4. E38 MAM treatment was used as a control, when layer 2-3 neurons are generated. The projections of ventrobasal thalamus into somatosensory cortex were studied using DiI injections. We found only subtle differences between groups (normal, E33, or E38 MAM-treated) in the thalamic afferent pattern on postnatal day 1 (P1) and P7. On P14, thalamic terminations distribute almost equally throughout the remaining cortical layers in the E33 MAM-treated group compared with normal and E38 MAM-treated animals, in which the ventrobasal thalamus projects primarily to central layers. Electrophysiological recordings conducted on mature ferrets treated with MAM on E33 demonstrated that somatotopic organization and receptive field size are normal. These findings emphasize the importance of layer 4 in determining the normal laminar pattern of thalamic termination and suggest that, although its absence is likely to impact on complex neocortical functional responses, topographic organization does not arise from the influence of layer 4.

Coincidence Detection or Temporal Integration? What the Neurons in Somatosensory Cortex Are Doing

To assess the impact of thalamic synchronization on cortical responsiveness, we used conditional cross-correlation analysis to measure the probability of neuronal discharges in somatosensory cortex as a function of the time between discharges in pairs of simultaneously recorded neurons in the ventrobasal thalamus. Among 26 neuronal trios, we found that thalamocortical efficacy after synchronous thalamic activity was nearly twice as large as the efficacy rate obtained when pairs of thalamic neurons discharged asynchronously. Nearly half of these neuronal trios displayed cooperative effects in which the cortical discharge probability after synchronous thalamic events was larger than could be predicted from the efficacy rate of individual thalamic discharges. In these cases of heterosynaptic cooperativity, thalamocortical efficacy declined to asymptotic levels when the interspike intervals were >6-8 msec. These results indicate that thalamic synchronization has a significant impact on cortical responsiveness and suggest that neuronal synchronization may play a critical role in the transmission of sensory information from one brain region to another.

Contribution of intralaminar thalamic nuclei to spike-and-wave-discharges during spontaneous seizures in a genetic rat model of absence epilepsy.

In an epileptic rat model of generalized absence epilepsies, the genetic absence epilepsy rats from Strasbourg (GAERS), simultaneous recordings of bilateral epidural electroencephalogram (EEG) of the prefrontal cortex and unit activity of neurons in the intralaminar centrolateral (CL) and paracentral thalamic nucleus (PC) were performed under neurolept-anaesthesia (fentanyl-dehydrobenzperidol analgesia). Spike-and-wave (SW) seizures in these rats are characterized by generalized 7-10 Hz spike-and-wave discharges (SWDs) on the EEG. All neurons recorded in intralaminar thalamic nuclei during spontaneous SWDs showed high-frequency (average 368 Hz, range 200-500 Hz), burst-like activity, which occurred in a highly synchronized fashion with every SWD or with alternating SWD-complexes. Burst discharges in intralaminar neurons were delayed by 13.1 ms (CL) and 12.7 ms (PC), with respect to the spike component of a given SWD on the EEG, whereas burst discharges in the ventrobasal thalamus (VB) and in the rostral nucleus reticularis thalami (rRT) preceded the spike component by 17.8 ms and 8.3 ms, respectively. The onset of SWDs on the EEG was preceded by a tonic firing pattern (20-50 Hz) in about one third of CL and PC neurons. Microiontophoretic application of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline aggravated, whereas, the glutamate receptor antagonists DNQX and APV dampened, SWD-related discharges in PC and CL; the GABAB receptor antagonist CGP 35347 had no measurable effect. These data indicate that intrathalamic nuclei are recruited rhythmically during SWDs, through mechanisms that seem to rely on a delayed glutamatergic excitation modulated by GABAergic influences, rather than a GABA-mediated rebound burst activity typical of relay cells. The finding of a temporal delay of SWD-related activity in intrathalamic, compared with "specific" thalamic relay nuclei, does not support the notion of a leading or pacemaker role in SWD generation. It is, however, rather suggestive of a function of intrathalamic neurons during synchronization and maintenance of neuronal oscillations, and these intrathalamic neurons may be recruited through glutamatergic corticofugal inputs.

Axonal conduction properties of antidromically identified neurons in rat barrel cortex

Physiological studies of the rodent somatosensory cortex have consistently described considerable heterogeneity in receptive field properties of neurons outside of layer IV, particularly those in layers V and VI. One such approach for distinguishing among different local circuits in these layers may be to identify the projection target of neurons whose axon collaterals contribute to the local network. In vivo, this can be accomplished using antidromic stimulation methods. Using this approach, the axonal conduction properties of cortical efferent neurons are described. Four projection sites were activated using electrical stimulation: (1) vibrissal motor cortex, (2) ventrobasal thalamus (VB), (3) posteromedial thalamic nucleus (POm), and (4) cerebral peduncle. Extracellular recordings were obtained from a total of 169 units in 21 animals. Results demonstrate a close correspondence between the laminar location of the antidromically identified neurons and their anatomically known layer of origin. Axonal properties were most distinct for corticofugal axons projecting through the crus cerebri. Corticothalamic axons projecting to either VB or POm were more similar to each other in terms of laminar location and conduction properties, but could be distinguished using focal electrical stimulation. It is concluded that, once stimulation parameters are adjusted for the small volume of the rat brain, the use of antidromic techniques may be an effective strategy to differentiate among projection neurons comprising different local circuits in supra- and infragranular circuits.

DOI-Induced Activation of the Cortex: Dependence on 5-HT2AHeteroceptors on Thalamocortical Glutamatergic Neurons

Administration of the hallucinogenic 5-HT(2A/2C) agonist 1-[2, 5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) induces expression of Fos protein in the cerebral cortex. To understand the mechanisms subserving this action of DOI, we examined the consequences of pharmacological and surgical manipulations on DOI-elicited Fos expression in the somatosensory cortex of the rat. DOI dose-dependently increased cortical Fos expression. Pretreatment with the selective 5-HT(2A) antagonist MDL 100,907 completely blocked DOI-elicited Fos expression, but pretreatment with the 5-HT(2C) antagonist SB 206,553 did not modify DOI-elicited Fos expression. These data suggest that DOI acts through 5-HT(2A) receptors to increase cortical Fos expression. However, we found that DOI did not induce Fos in cortical 5-HT(2A) immunoreactive neurons but did increase expression in a band of neurons spanning superficial layer V to deep III, within the apical dendritic fields of layer V 5-HT(2A)-immunoreactive cells. This band of Fos immunoreactive neurons was in register with anterogradely labeled axons from the ventrobasal thalamus, which have previously been shown to be glutamatergic and express the 5-HT(2A) transcript. The effects of DOI were markedly reduced in animals pretreated with the AMPA/KA antagonist GYKI 52466, and lesions of the ventrobasal thalamus attenuated DOI-elicited Fos expression in the cortex. These data suggest that DOI activates 5-HT(2A) receptors on thalamocortical neurons and thereby increases glutamate release, which in turn drives Fos expression in cortical neurons through an AMPA receptor-dependent mechanism. These data cast new light on the mechanisms of action of hallucinogens.

Novel mode of nitric oxide neurotransmission mediated via S-nitroso-cysteinyl-glycine.

S-nitroso-cysteinyl-glycine, a novel nitric oxide-adduct thiol compound, can be detected in the brain (2.3+/-0.6 pmol/mg protein), and released following stimulation of sensory afferents to the rat ventrobasal thalamus in vivo (resting conditions 17 nM; stimulation: 186 nM). Iontophoretic application of CysNOGly (20-80 nA) onto thalamic neurons in vivo resulted in enhancements of excitatory responses to either NMDA or AMPA (182+/-13.6% and 244+/-27.8% of control values, n = 15). CysNOGly enhanced responses to stimulation of vibrissal afferents to 132+/-2.2% (n = 7) of control values. In contrast, the dipeptide CysGly reduced responses of ventrobasal neurons to NMDA and AMPA (54+/-8.4% and 55+/-10.8% of control, n = 5). CysNOGly was also a potent activator of soluble guanylate cyclase in vitro. Moreover, we found that NMDA elevated CysNOGly levels in vitro and this stimulatory effect was reduced by inhibitors of the neuronal NO synthase and of the gamma-glutamyl transpeptidase, suggesting that production of NO and CysGly is a prelude to CysNOGly synthesis. These findings suggest that the nitrosothiol CysNOGly plays a role in synaptic transmission in the ventrobasal thalamus. We propose a novel synaptic buffering mechanism where S-nitroso-cysteinyl-glycine serves to restrict the locus of action of nitric oxide and so increase its local availability for target delivery. This could lead to a change in neuronal responses favouring sensory transmission similar to that seen in wakefulness or arousal in order to locally enhance transmission of persistent sensory stimuli.

Contributions of mGlu1 and mGlu5 receptors to interactions with N-methyl-d-aspartate receptor-mediated responses and nociceptive sensory responses of rat thalamic neurons

The nociceptive responses of rat ventrobasal thalamus neurons can be reduced by N-methyl-d-aspartate antagonists and by selective metabotropic glutamate receptor mGlu1 antagonists. The recent development of the mGlu5-selective antagonist 6-methyl-2-(phenylethynyl)-pyridine now allows the direct probing of the possible involvement of mGlu5 receptors in thalamic nociceptive responses. Extracellular recordings were made from single neurons in the ventrobasal thalamus and immediately overlying dorsal thalamic nuclei of adult urethane-anaesthetized rats using multi-barrel electrodes. Responses of neurons to iontophoretic applications of the mGlu5-selective agonist (R,S)-2-chloro-5-hydroxyphenylglycine were selectively reduced during continuous iontophoretic applications of 6-methyl-2-(phenylethynyl)-pyridine. Similar applications of 6-methyl-2-(phenylethynyl)-pyridine reduced neuronal responses to noxious thermal stimuli to 53±9.5% of control responses. Co- application by iontophoresis of N-methyl-d-aspartate and metabotropic glutamate receptor agonists resulted in a mutual potentiation of excitatory responses. This effect could be reduced by either 6-methyl-2-(phenylethynyl)-pyridine or the mGlu1 antagonist LY367385.These results, taken together with previous data, suggest that acute thalamic nociceptive responses are mediated by a combination of mGlu1, mGlu5 and N-methyl-d-aspartate receptor activation, and that co-activation of these receptors produces a synergistic excitatory effect. Thus blockade of any of these receptor types would have a profound effect on the overall nociceptive response.

Projections of the Parabrachial Nucleus in the Old World Monkey

The efferent projections of the pontine parabrachial nucleus (PBN) were examined in the Old World monkey (Macaca fascicularis) using tritiated amino acid autoradiography and horseradish peroxidase histochemistry. Parabrachiofugal fibers ascended to the forebrain along three pathways: the central tegmental tract, the ventral ascending catecholaminergic pathway, and a pathway located on the midline between the medial longitudinal fasciculi. The PBN projected heavily to the central nucleus of the amygdala and the lateral division of the bed nucleus of the stria terminalis and moderately to the ventral tegmental area and the substantia nigra. Light terminal label also was present within the dorsomedial, ventromedial, lateral, supramammillary, and infundibular nuclei of the hypothalamus and the annular nucleus and the dorsal raphe nucleus within the brain stem. The overall pattern of terminal label was similar to that previously reported for nonprimate species, but several differences were notable. In monkey the projection to the ventrobasal thalamus did not coincide with the region that contains gustatory-responsive neurons. In rats, these parabrachiothalamic fibers convey gustatory activity but in the monkey these fibers may carry visceral afferent information. The projections from the PBN to the hypothalamus in the monkey were neither as widespread nor as intense as in the rat, and the monkey lacks a projection from the PBN to the frontal and insular cortices.

Somatostatin inhibits GABAergic transmission in the sensory thalamus via presynaptic receptors

The action of somatostatin on GABA-mediated transmission was investigated in cat and rat thalamocortical neurons of the dorsal lateral geniculate nucleus and ventrobasal thalamus in vitro. In the cat thalamus, somatostatin (10 μM) had no effect on the passive membrane properties of thalamocortical neurons and on the postsynaptic response elicited in these cells by bath or iontophoretic application of (±)baclofen (5–10 μM) or GABA, respectively. However, somatostatin (1–10 μM) decreased by a similar amount (45–55%) the amplitude of electrically evoked GABA A and GABA B inhibitory postsynaptic potentials in 71 and 50% of neurons in the lateral geniculate and ventrobasal nucleus, respectively. In addition, the neuropeptide abolished spontaneous bursts of GABA A inhibitory postsynaptic potentials in 85% of kitten lateral geniculate neurons, and decreased (40%) the amplitude of single spontaneous GABA A inhibitory postsynaptic potentials in 87% of neurons in the cat lateral geniculate nucleus. Similar results were obtained in the rat thalamus. Somatostatin (10 μM) had no effect on the passive membrane properties of thalamocortical neurons in this species, or on the outward current elicited by puff-application of (±)baclofen (5–10 μM). However, in 57 and 22% of neurons in the rat lateral geniculate and ventrobasal nuclei, respectively, somatostatin (1 μM) reduced the frequency, but not the amplitude, of miniature GABA A inhibitory postsynaptic currents by 31 and 37%, respectively. In addition, the neuropeptide (1 μM) decreased the amplitude of evoked GABA A inhibitory postsynaptic currents in 20 and 55% of rat ventrobasal neurons recorded in normal conditions and during enhanced excitability, respectively: this effect was stronger on bursts of inhibitory postsynaptic currents(100% decrease) than on single inhibitory postsynaptic currents (41% decrease). These results demonstrate that in the sensory thalamus somatostatin inhibits GABA A- and GABA B-mediated transmission via a presynaptic mechanism, and its action is more prominent on bursts of GABAergic synaptic currents/potentials.

Persistent depolarization and Glu uptake inhibition operate distinct osmoregulatory mechanisms in the mammalian brain

The ways of coupling neuronal with glial compartments in natural physiology was investigated in microdialysis experiments by monitoring extracellular concentration of amino acids in the brain of anaesthetized rats. We hypothesized that extracellular [Glu], [Gln] and [Tau] patterns would be state-dependent. This was tested by stimulation of N-methyl- d-aspartate (NMDA) receptors, by inhibition of Glu uptake or by local depolarization with a high-K + dialysate, coupled with the addition of Co 2+ to block Ca 2+ influx. The results showed that (1) extracellular [Gln] was low whereas [Glu] and [Tau] were high during infusion of NMDA (0.5–1.0 mM) or high-K + (80 mM) in the hippocampus and ventrobasal thalamus, (2) hippocampal extracellular [Glu], [Gln] and [Tau] were increased in response to the Glu uptake inhibitor, l- trans-pyrrolidine-2,4-dicarboxilic acid ( tPDC, 0.5–3.0 mM), in a concentration-dependent manner, (3) high-K +-induced increase of extracellular [Glu] was partially blocked by the addition of 10 mM CoCl 2 with the high-K + dialysate in the hippocampus. Searching for main correlations between changes in [Glu], [Gln] and [Tau] by calculating partial correlations and with the use of factor analyses we found, the primary response of the mammalian brain to persistent depolarization is the neuronal uptake of [Gln] and release of [Tau] thereupon, acting independently of Glu changes. When glial and neuronal uptake of Glu is blocked, releases of Tau occur from neuronal as well as glial compartments accompanied by increases of [Gln] in the mammalian brain.

The influence of single VB thalamocortical impulses on barrel columns of rabbit somatosensory cortex.

Extracellular recordings were obtained from single neurons in ventrobasal (VB) thalamus of awake rabbits while field potentials were recorded at various depths within topographically aligned and nonaligned barrel columns of somatosensory cortex (S1). Spike-triggered averages of cortical field potentials were obtained following action potentials in thalamic neurons. Action potentials in a VB neuron elicited a cortical response within layer 4 with three distinct components. 1) A biphasic, initially positive response (latency <1 ms) was interpreted to reflect activation of the VB axon terminals (the AxTP). This response was not affected by infusion of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist within the barrel. In contrast, later components of the response were completely eliminated and were interpreted to reflect focal synaptic potentials. 2) A negative potential [focal synaptic negativity (FSN)] occurred at a mean latency of 1.65 ms and lasted approximately 4 ms. This response had a rapid rise time ( approximately 0.7 ms) and was interpreted to reflect monosynaptic excitation. 3) The third component was a positive potential (the FSP), with a slow rise time and a half-amplitude duration of approximately 30 ms. The FSP showed a weak reversal in superficial cortical layers and was interpreted to reflect di/polysynaptic inhibition. The amplitudes of the AxTP, the FSN, and the FSP reached a peak near layer 4 and were highly attenuated in both superficial and deep cortical layers. All components were attenuated or absent when the cortical electrode was missaligned from the thalamic electrode by a single cortical barrel. Deconvolution procedures revealed that the autocorrelogram of the presynaptic VB neuron had very little influence on either the amplitude or duration of the AxTP or the FSN, and only a minor influence (mean, 11%) on the amplitude of the FSP. We conclude that individual VB thalamic impulses entering a cortical barrel engage both monosynaptic excitatory and di/polysynaptic inhibitory mechanisms. Putative inhibitory interneurons of an S1 barrel receive a highly divergent/convergent monosynaptic input from the topographically aligned VB barreloid, and this results in sharp synchrony among these interneurons. We suggest that single-fiber access to disynaptic inhibition is facilitated by this sharp synchrony, and that the FSP reflects a consequent synchronous wave of feed-forward inhibition within the S1 barrel.

Baroreceptive and somatosensory convergent thalamic neurons project to the posterior insular cortex in the rat

Connectivity between the rat posterior insula and the ventrobasal thalamus has been demonstrated anatomically. Neurons convergent for baroreceptor and nociceptive input have also been identified in the homologous anterior insula of the primate. Whether similar convergent cells exist in the ventrobasal thalamus was investigated in 30 urethane anesthetized male Sprague–Dawley rats. Six classes of cells were identified in the right ventrobasal thalamus: (a) 83/159 (52%) baroreceptive and nociceptive convergent units; (b) 2/159 (1%) convergent cells responding to baroreceptor activation and light touch; (c) 44/159 (28%) purely nociceptive units; (d)10/159 (6%) purely baroreceptive units; (e) 1/159 (0.6%) cells responding to brush alone and (f) 19/159 (12%) unresponsive units. Of the viscerosomatic convergent cells, 66/85 (78%) were situated in the ventroposterolateral nucleus (VPL), 6/85 (7%) in the ventroposterolateral parvicellular nucleus (VPLpc), and 13/85 (15%) in the ventroposteromedial nucleus (VPM). Fifteen right ventrobasal thalamic units were antidromically activated and 34 units orthodromically activated by right posterior insular microstimulation. Cobalt injection into the right ventrobasal thalamus blocked the right insular response to baroreceptor activation by >70%. These data indicate: (a) baroreceptive and somatosensory nociceptive convergent units exist in the ventrobasal thalamus; (b) thalamic convergent neurons project directly to the ipsilateral posterior insula and receive reciprocal insulothalamic projections; and (c) a significant proportion of baroreceptor input relays to the posterior insula through the ipsilateral ventrobasal thalamus.

A mapping label required for normal scale of body representation in the cortex.

The neocortical primary somatosensory area (S1) consists of a map of the body surface. The cortical area devoted to different regions, such as parts of the face or hands, reflects their functional importance. Here we investigated the role of genetically determined positional labels in neocortical mapping. Ephrin-A5 was expressed in a medial > lateral gradient across S1, whereas its receptor EphA4 was in a matching gradient across the thalamic ventrobasal (VB) complex, which provides S1 input. Ephrin-A5 had topographically specific effects on VB axon guidance in vitro. Ephrin-A5 gene disruption caused graded, topographically specific distortion in the S1 body map, with medial regions contracted and lateral regions expanded, changing relative areas up to 50% in developing and adult mice. These results provide evidence for within-area thalamocortical mapping labels and show that a genetic difference can cause a lasting change in relative scale of different regions within a topographic map.

Regionally selective blockade of GABAergic inhibition by zinc in the thalamocortical system: functional significance.

The thalamocortical (TC) system is a tightly coupled synaptic circuit in which GABAergic inhibition originating from the nucleus reticularis thalami (NRT) serves to synchronize oscillatory TC rhythmic behavior. Zinc is colocalized within nerve terminals throughout the TC system with dense staining for zinc observed in NRT, neocortex, and thalamus. Whole cell voltage-clamp recordings of GABA-evoked responses were conducted in neurons isolated from ventrobasal thalamus, NRT, and somatosensory cortex to investigate modulation of the GABA-mediated chloride conductance by zinc. Zinc blocked GABA responses in a regionally specific, noncompetitive manner within the TC system. The regional levels of GABA blockade efficacy by zinc were: thalamus > NRT > cortex. The relationship between clonazepam and zinc sensitivity of GABA(A)-mediated responses was examined to investigate possible presence or absence of specific GABA(A) receptor (GABAR) subunits. These properties of GABARs have been hypothesized previously to be dependent on presence or absence of the gamma2 subunit and seem to display an inverse relationship. In cross-correlation plots, thalamic and NRT neurons did not show a statistically significant relationship between clonazepam and zinc sensitivity; however, a statistically significant correlation was observed in cortical neurons. Spontaneous epileptic TC oscillations can be induced in vitro by perfusion of TC slices with an extracellular medium containing no added Mg(2+). Multiple varieties of oscillations are generated, including simple TC burst complexes (sTBCs), which resemble spike-wave discharge activity. A second variant was termed a complex TC burst complex (cTBC), which resembled generalized tonic clonic seizure activity. sTBCs were exacerbated by zinc, whereas cTBCs were blocked completely by zinc. This supported the concept that zinc release may modulate TC rhythms in vivo. Zinc interacts with a variety of ionic conductances, including GABAR currents, N-methyl-D-aspartate (NMDA) receptor currents, and transient potassium (A) currents. D-2-amino-5-phosphonovaleric acid and 4-aminopyridine blocked both s- and cTBCs in TC slices. Therefore NMDA and A current-blocking effects of zinc are insufficient to explain differential zinc sensitivity of these rhythms. This supports a significant role of zinc-induced GABAR modulation in differential TC rhythm effects. Zinc is localized in high levels within the TC system and appears to be released during TC activity. Furthermore application of exogenous zinc modulates TC rhythms and differentially blocks GABARs within the TC system. These data are consistent with the hypothesis that endogenously released zinc may have important neuromodulatory actions impacting generation of TC rhythms, mediated at least in part by effects on GABARs.

Descending corticofugal neurons in layer 5 of rabbit S1: evidence for potent corticocortical, but not thalamocortical, input.

Extracellular recordings were obtained from descending corticofugal neurons of layer 5 (CF-5 neurons) in primary somatosensory cortex (S1) of awake rabbits. These cells were identified by antidromic activation via stimulation sites in ventrobasal (VB) thalamus. Recordings were also obtained from putative GABA-ergic interneurons (suspected inhibitory interneurons, SINs) located in the same microelectrode penetrations, and in close proximity (+/- 300 microns) to the CF-5 neurons. In some experiments, the above populations were recorded simultaneously with neurons in the topographically aligned VB thalamic barreloid. Each of several experimental strategies failed to reveal evidence of monosynaptic thalamic input to CF-5 neurons, but revealed a clear monosynaptic input to neighboring SINs: (1) whereas CF-5 neurons responded at very long synaptic latencies to intense electrical stimulation of VB thalamus, neighboring SINs responded at short latencies; (2) whereas cross-correlations between CF-5 neurons and topographically aligned VB neurons failed to show significant peaks indicative of monosynaptic VB input, neighboring SINs did show such peaks; and (3) whereas CF-5 neurons were unresponsive to microstimulation of topographically aligned VB thalamic barreloids, neighboring SINs were very responsive to such stimulation. Both CF-5 neurons and neighboring SINs responded to electrical stimulation of the corpus callosum with a robust, short-latency synaptic response. This finding demonstrates that CF-5 neurons are capable of vigorous, short-latency responses to excitatory synaptic input. These data suggest considerable specificity in the thalamocortical connectivity of subpopulations within layer 5, and support the notion that CF-5 neurons are dominated by corticocortical rather than thalamocortical input.

Microglial and astrocytic reactions prior to onset of thalamic cell death after traumatic lesion of the rat sensorimotor cortex

The temporospatial relationship between microglial and astrocytic reactions and delayed thalamic cell death was examined 1-7 days following a traumatic cold lesion of the rat sensorimotor cortex using immunocytochemistry in combination with terminal deoxynucleotidyltransferase-mediated biotinylated dUTP nick end labeling (TUNEL) of nuclear DNA fragmentation. No or only occasional TUNEL-positive cells were found in the thalamic relay nuclei up to 3 days after trauma. After 7 days, on the other hand, a considerable number of TUNEL-positive cells were seen in the ventrobasal, the ventrolateral and posterior thalamic nuclei. Already 3 days after trauma, i.e., before cell injury was detectable, many protoplasmic astrocytes, which were reactive for glial fibrillary acidic protein, and ramified microglia, which were positive for complement receptor type 3b (CR3b) but negative for major histocompatibility complex (MHC) class II antigen, were noticed in the thalamus. The number of labeled astro- and microglia further increased after 7 days, when DNA fragmentation became evident. At this time, the morphology of microglia shifted towards bushy and rod-like cells, and microglia became also reactive for MHC class II antigen. Clusters of CR3b- and MHC class II-positive microglia were found in the ventrobasal thalamus. The present findings demonstrate that trauma-induced microglial and astrocytic reactions appear in the thalamus prior the onset of cell damage.

Attention-related, cross-modality modulation of somatosensory neurons in primate ventrobasal (VB) thalamus

Attention-related modulation (AM) of the somatosensory responses of single neurons has been demonstrated in the cerebral cortex and medullary dorsal horn, but not in the ventrobasal thalamus. The somatically evoked activity was recorded of single units in the ventral posterior lateral thalamus (VPL) of awake monkeys while they detected the termination of task-relevant somatic or visual stimuli. Eighteen of 56 somatically responsive VPL neurons are reported that were recorded for enough time for a complete analysis of their responses during both the visual and somatic attention tasks. All neurons were spontaneously active and responded either to innocuous cutaneous (13/18) or deep (5/18) stimuli. Seven neurons (7/18, 38.8%) showed AM of somatosensory responsiveness. Two cells (2/7, 28.6%) showed AM only during the visual task, two others (2/7, 28.6%) only during the somatosensory task, and three cells (3/7, 42.8%) showed AM during both tasks. All five cells showing AM during the somatosensory task had enhanced responses to the task-relevant somatic stimulus. In contrast, the somatosensory responses of all five cells showing AM during the visual task were reduced. It is concluded that selective attention is associated with a modality specific modulation of the somatosensory responses of a sub-population of neurons within the primate VPL nucleus.

Neurotrophin receptor (p75) in the trigeminal thalamus of the rat: development, response to injury, transient vibrissa-related patterning, and retrograde transport.

We report on the transient, patterned expression of p75 in the ventrobasal (VB) thalamus, the major thalamic relay for somatosensation. We immunostained the brains of developing rats ranging in age from embryonic day (E) 14.5 to postnatal day (PD) 15 with an antibody against p75. To compare p75 expression with the developing synaptic organization within VB, we also immunolocalized the synaptic-vesicle-associated protein, synaptophysin (SYN), on alternate sections. p75-immunoreactivity (IR) was dense and uniform in the ventroposterior medial nucleus (VPM) in the late embryonic and early postnatal periods (E 16.5 to PD 3). In contrast, from PD 4-10, p75-IR in the VPM was patterned, reminiscent of cytochrome-oxidase-stained barreloids, a characteristic feature of the VB in rodents. By PD 14, p75-IR in the VPM was no longer detectable. The ventroposterior lateral nucleus (VPL), in contrast, exhibited no p75-IR. No p75-IR was detected in the ventroposterior lateral nucleus (VPL) at any developmental stage in which VPM could be distinguished from VPL. Light, but clearly patterned SYN-IR, first detectable on PD 2-3, increased in intensity in both VPL and VPM through PD 15. Sectioning the infraorbital nerve on PD 0 resulted in blurred patterns of p75- and SYN-IR within VPM in PD 7-9 rat pups. Removing large portions of the somatosensory cortex on PD 0 resulted in subsequent greatly reduced p75- and SYN-IR within VB. To specify the source of the p75-IR terminals, we stereotaxically injected into the VPM of PD 4-5 rats a monoclonal antibody to p75. One to 2 days later, IR of retrogradely transported p75 antibodies could be traced within axons and cell bodies of neurons associated with the trigeminothalamic pathway through the caudal diencephalon and mesencephalon; labelling was confined to the contralateral trigeminal principal sensory nucleus. The observed, transiently patterned p75-IR in VPM the early postpartum period suggests a role for p75 in synaptogenesis and pattern formation.

Corticostriatal Projections from Rat Barrel Cortex Have an Anisotropic Organization that Correlates with Vibrissal Whisking Behavior

To elucidate the detailed organization of corticostriatal projections from rodent somatosensory cortex, the anterograde tracers biotinylated dextran amine (BDA) and fluoro-ruby (FR) were injected into separate parts of the whisker "barrel" representation. In one group of rats, the two tracers were injected into different barrel columns residing in the same row; in the other group of rats, the tracers were deposited into barrel columns residing in different rows. Reconstructions of labeled axonal varicosities in the neostriatum and ventrobasal thalamus were analyzed quantitatively to compare the extent of overlapping projections to these subcortical structures. For both groups of animals, corticostriatal projections terminated in densely packed clusters that occupied curved lamellar-shaped regions along the dorsolateral edge of the neostriatum. When the tracers were injected into different whisker barrel rows, the distribution of BDA- and FR-labeled terminals in the neostriatum followed a crude somatotopic organization in which the amount of overlap was approximately the same as in the ventrobasal thalamus. When both tracers were injected into the same whisker barrel row, however, the amount of corticostriatal overlap was significantly higher than the amount of overlap observed in the ventrobasal thalamus. These results indicate that corticostriatal projections from whisker barrel cortex have an anisotropic organization that correlates with the pattern of vibrissal movements during whisking behavior.