Responses Of Thalamic Neurons Research Articles

Chapter 33 Neuronal signals of importance to the performance of visual recognition memory tasks: evidence from recordings of single neurones in the medial thalamus of primates

Publisher Summary The chapter discusses the activity of single neurones recorded within the medial thalamus of monkeys during their performance of recognition memory tasks with the objective of discovering what information relating to recognition memory neurones of the MD and MID nuclei might signal. A further objective is to compare the responses of such thalamic neurones with those found in the medial temporal lobes. The experiments performed demonstrated the presence of neuronal activity that encodes information about the previous occurrence of stimuli in the magnocellular division of the mediodorsal nucleus and the caudal part of the paraventricular midline nucleus of the medial thalamus. The conjunction of these results with the findings of lesion studies demonstrates the importance of these parts of the medial thalamus for processes necessary for recognition memory. The findings for the medial thalamus are considered in relation to those in other areas, particularly the medial temporal lobe and basal forebrain, areas that lesion experiments indicate is necessary for performance of recognition memory tasks. It is concluded that these interconnected areas form part of the system allowing the discrimination of the recency of occurrence and familiarity of stimuli.

Convergence of olfactory and nasotrigeminal inputs and possible trigeminal contributions to olfactory responses in the rat thalamus

To elucidate the role of trigeminal input on the olfactory system, field-evoked potentials were measured following electrical stimulation of the nasociliary branch of the trigeminal nerve in the olfactory-related structures in the rat brain. Significant potential changes were recorded in the mediodorsal nucleus of the thalamus and the lateral hypothalamic area. In the mediodorsal nucleus of the thalamus, the neurons responding to olfactory bulb electrical stimulation also responded to trigeminal nerve stimulation. Single neuronal responses of mediodorsal thalamic neurons following odorant stimulation were enhanced by blockade of the trigeminal nerve with procaine. These results suggest that olfactory and trigeminal pathways converge on the same neural elements within the mediodorsal nucleus of the thalamus and that the trigeminal input may modulate olfactory input in this nucleus.

Responses of cat ventroposterolateral thalamic neurons to vibrotactile stimulation of forelimb footpads.

Responses of neurons in the ventroposterolateral nucleus of the thalamus to vibration applied to the forelimb footpads were analyzed in anesthetized cats in order to describe the signalling properties of thalamic neurons that received input from the different classes of tactile afferents innervating the glabrous skin of the distal forelimb. Seventy-six thalamic neurons, the majority of which (60 of 76) were positively identified as thalamocortical projection neurons, were classified into two broad groups according to their responses to 1-s step indentations of the skin. A minority (24%) comprised neurons that had slowly adapting (SA) responses, whereas the remainder (76%), the dynamically sensitive neurons, had transient responses to the onset and offset phase of the step and were further classified according to their sensitivity to cutaneous vibrotactile stimuli into those activated by low-frequency vibration (rapidly adapting, RA, neurons) and those activated by high frequencies (Pacinian afferent, PC, neurons). Thalamic RA neurons displayed phaselocked responses to vibration at frequencies up to approximately 100 Hz, while PC neurons displayed phaselocked responses to vibration up to 400-500 Hz. Thalamic SA neurons varied in their responses to vibrotactile stimuli; half were most sensitive to vibration frequencies of 50 Hz or less, while the others responded over a broader range of frequencies. Although three major classes of footpad-related thalamic neurons were identified, there was evidence of convergent input to a small proportion of them. The study demonstrates that thalamic neurons have the capacity for responding to cutaneous vibration with phaselocked, patterned impulse trains, which would enable them to encode information about vibrotactile frequencies up to approximately 300 Hz.

Knee joint input into the peripheral region of the ventral posterior lateral nucleus of cat thalamus.

1. Experiments were carried out in chloralose-anesthetized cats to study the responses of neurons in the lateral thalamus to excitation of afferent fibres from the knee joint. 2. Single- and multi-unit recordings were made with tungsten electrodes in dorsoventral penetrations through the ventral posterior lateral nucleus (VPL) during electrical stimulation of the medial articular nerve (MAN) of the cat's knee joint at an intensity sufficient to excite slowly conducting unmyelinated fibers. The locations of the recording sites were verified by recovering electrolytic lesion sites in histological sections (Nissl and cytochrome oxidase staining). 3. The average earliest latency for excitation of thalamic responses was 19.1 +/- 8.5 (SD) ms (n = 50). The threshold for excitation of most thalamic units was found to correspond to peripheral joint afferent fibers of the A-delta group. 4. The majority of neurons responding to MAN stimulation were found to be dorsal or ventral to the low-threshold cutaneous hindlimb region of the lateral division of the VPL (stereotaxic coordinates: AP 9.0-11.5; ML 7.0-9.5). In the ventral periphery of the VPL, most neurons responding to MAN stimulation (11/14) were wide dynamic range (WDR) with a discrete cutaneous receptive field on the hindpaw digits. Six WDR neurons were found dorsal to the hindlimb VPL with a convergent receptive field on the hindlimb (but not hindpaw digits). No nociceptive-specific knee joint units were found. 5. Other neurons were found dorsal to the hindlimb VPL with large receptive fields often encompassing the whole contralateral leg, including skin and deep hindlimb structures, possibly in a region described as the dorsal portion of the posterior complex (POd). Some neurons were found with no receptive field. 6. This study provides the first observations on the responses of lateral thalamic neurons to stimulation of the MAN of the cat knee joint. These results demonstrate a central pathway conveying impulses from specific deep joint afferents of the MAN to the peripheral region of the VPL and overlying region known as the POd, regions implicated in the transmission of nociceptive information.

The possible involvement of excitatory amino acids and NMDA receptors in thalamic pain mechanisms and central pain syndromes

T he possibility that the ventrobasal complex of the thalamus is involved in the generation of central pain syndromes (CPS) is an intriguing hypothesis. Dr. Lenz argues that the abnormal bursting firing patterns seen in the ventrobasal complex of patients with CPS is, in some way, enabled fol lowing interruption of peripheral input, and that this induces CPS. Furthermore, Dr. Lenz suggests that excitatory amino acids, and NMDA receptors in particular, may be involved in acute thalamic pain mechanisms and perhaps also in CPS. The focus article by Dr. Lenz puts some of the arguments in favor of this idea very cogently. There are two related questions that I propose to focus upon here: first, are exitatory amino acids (and NMDA receptors in particular) involved in the acute processing of nociceptive information in the thalamus? Second, if so, how does this relate to the generation of CPS? Pharmacological experiments from this laboratory indicate that excitatory amino acid receptors, particularly those of the NMDA type, are involved in acute nociceptive responses of rat thalamic neurons (including ventrobasal complex neurons). 6 The identity of the transmitter(s) mediating these responses is still unclear, as highlighted by Dr. Lenz, although Lglutamate is a likely contender for this role 3,9 in spite of the lack of retrograde amino acid transport in sensory afferents to the thalamus. Other possibil it ies exist, however, that could account for the susceptibility of thalamic nociceptive responses to NMDA an-

Effects of Morphine on Responses of Nociceptive Ventrobasal Thalamic Neurons in Diabetic Rats

The influence of diabetes on the effects of morphine on the responses of ventrobasal (VB) thalamic neurons to mechanical noxious stimuli were studied in chloral hydrate-anesthetized rats. Animals were rendered diabetic by an injection of streptozotocin (60 mg/kg, i.v.). Morphine (0.3 mg/kg), administered i.v., produced a reduction in the responsiveness of VB thalamic neurons to noxious stimulation in control rats. This effect was reversed by naloxone. In contrast, the inhibitory effects of morphine on the nociceptive responses of VB thalamic neurons were significantly attenuated in diabetic rats, as compared with the controls. However, there were no significant differences in inhibitory potency between diabetic and control rats when morphine (30 nM) was administered intrathecally. It seems likely that these changes in the sensitivity of VB thalamic neurons to morphine are, to some extent, the source of the reduction in the analgesic efficacy of morphine in diabetic rats.

Sensory responses of intralaminar thalamic neurons activated by the superior colliculus.

The intralaminar thalamus of anesthetized rats was explored for neurons activated by stimulation of the superior colliculus and responsive to sensory inputs. Neurons activated by stimulation of the intermediate and deep collicular layers were distributed throughout the intralaminar thalamus. Approximately one half of them responded to tectal as well as sensory inputs. The majority were nociceptive or had a more complex response pattern including responses to auditory stimulation. A small population of low threshold units had contralateral orofacial receptive fields and responded to light taps; these units were preferentially localized anteriorly in the central lateral and paracentral nuclei. Neurons responsive to tectal and sensory stimulation were randomly intermingled with other neurons which had no detectable sensory input. The results indicate that ascending projection neurons of the intermediate and deep layers of the superior colliculus provide an input to functionally diverse subpopulations of intralaminar thalamic neurons. In view of its projections to motor cortex and basal ganglia, the intralaminar thalamus appears directly implicated in basal ganglia and superior colliculus related mechanisms of attention, arousal and postural orienting.

Electrophysiological evidence that morphine can exert an antinociceptive effect in a neuropathic state: a study in the ventrobasal thalamus of rats after moderate ligation of one sciatic nerve

This study was performed in rats with a mononeuropathy induced by loose ligatures around the common sciatic nerve 2 weeks before the recording session, and exhibiting clear alterations of several pain-related behaviours. Morphine injected intravenously (0.6 and 1 mg/kg) strongly depressed the ventrobasal thalamic neuronal responses to pinch applied to the lesioned or the non-lesioned hindpaw. The effect, comparable on the both sides, was dose-related and reversed by naloxone (0.1 mg/kg i.v.).

Involvement of supraspinal and spinal segmental alpha-2-adrenergic mechanisms in the medetomidine-induced antinociception

The effect of systemically administered medetomidine, a selective alpha-2-adrenoceptor agonist, was studied by electrophysiological recordings of the peripherally evoked responses of three different types of sensory neuronal populations in the rat: medial thalamic neurons exclusively responding to mechanical cutaneous stimuli at noxious intensities, spinothalamic tract neurons of the spinal cord responding exclusively or differentially to mechanical cutaneous stimuli at noxious intensities, and low-threshold mechanoreceptive spinal dorsal horn neurons with ascending projections. The neuronal effects were compared with the behavioral data obtained in mechanically and thermally induced nociceptive tail reflex tests in intact and spinal rats. A reversal of the antinociceptive effects was attempted by systemically (1.5mg/kg, i.p.) or intrathecally (25 μ g) administered atipamezole, a selective alpha-2-adrenoceptor antagonist. Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons. A lower dose of medetomidine was needed to suppress significantly (half-maximally) evoked responses of the nociceptive medial thalamic neurons (100/μg/kg) than those of the nociceptive spinothalamic tract neurons (300 μg/kg). The decrease of evoked responses of the nociceptive spinothalamic tract neurons was accompanied by a decrease in spontaneous activity. The responses of the low-threshold mechanoreceptive projection neurons of the spinal cord were not influenced by medetomidine (30–300 μg/kg). The reflex studies with a (anesthetic) medetomidine dose of 300 μg/kg indicated that in intact and otherwise drug-free rats, medetomidine produced a significant prolongation of the nociceptive reflex response latency to a tail-pinch and heat; these antinociceptive effects of systemic medetomidine were reversed by systemically and intrathecally applied atipamezole. In spinal rats systemically applied medetomidine (300 μg/kg) also produced a significant prolongation of the tail-flick latency, which was reversed by systemically applied atipamezole. The results suggest that a high anesthetic dose of systemically applied medetomidine (300/μg/kg) can suppress nociceptive sensory neuronal and reflex responses due to spinal segmental mechanisms through an action on alpha-2-adrenoceptors. This spinal effect is selective to responses of nociceptive neurons, and at least partly postsynaptic as indicated by the concomitant decrease in spontaneous activity. At a lower, subanesthetic (but sedative) dose (100 μg/kg) the antinociceptive effect of systemically applied medetomidine can be explained by supraspinal alpha-2-adrenergic mechanisms.

Focal Dorsal Raphe Stimulation and Pinnal Electrical Stimulation Modulate Spontaneous and Noxious Evoked Responses in Thalamic Neurons

This study investigated the nocieceptive responses of single neurons within the nucleus parafascicularis (PF) thalami of the rat following two modes of electrical stimulation known to induce analgesia. It was found that both focal electrical dorsal raphe stimulation (DRS) and bilateral pinnal (ear) electrical stimulation (PES) converge on the same PF neurons, affecting both the spontaneous discharges and the noxious evoked responses toward these neurons. The effects of different stimulus current intensity, frequency and pulse duration were also examined. It was found that for both DRS and PES at pulse frequency of 10 Hz and current amplitude of 10 microA are the optimal parameters to modulate both the spontaneous and the noxious evoked responses. These stimuli produced prolonged effects related to the duration of stimulation. The external (PES) low current stimulation which was delivered below the sensory threshold was as effective in modulating noxious responses as the invasive DRS in intact animals and in animals with bilateral dorsolateral-funiculus ablation. It was observed that dorsal lateral funiculus ablation (DLFx) did not modify the DRS and the PES effects. These observations further support the existence of an ascending pain modulation pathway.

The G. L. Brown lecture. Adventures in anaesthesia

The results presented in this lecture show that anaesthetic agents impede the transfer of information from the periphery to the cerebral cortex. This is shown both as a reduction in the amplitudes of the initial positive and negative waves of the cerebral cortical response evoked by simulation of the periphery and as an increase in the latency of this response. This effect is most probably a prime effect of anaesthesia since (a) it is common to all the anaesthetics used, (b) the potency of the anaesthetics is directly proportional to their lipid solubility, and (c) the effect is reversed by high ambient pressures. The major site at which information transfer is most susceptible to the action of anaesthetics is at the level of the ventrobasal thalamus, although the cells in cortical layer V also appear to have an enhanced susceptibility to anaesthetic action. This latter observation is seen both in whole animal and cortical slice preparations. None the less, the first site of synaptic transfer at which anaesthetics exert a profound effect is upon the monosynaptically generated responses of ventrobasal thalamic neurones to cuneothalamic input. A possible mechanism of action for anaesthetic agents acting at this site would be upon a hypothetical cortico-thalamic-reticular-thalamic loop with the theoretical ability to control the responsiveness of the ventrobasal thalamic cells. This action was proposed both from the activity of neurones in response to anaesthetic agents and the anatomical arrangement seen in the thalamus. The thalamic reticular nucleus is a curved sheath of cells situated between the internal capsule and the external medullary lamina, capping and bounding laterally the specific nuclei of the dorsal thalamus. There is both anatomical and physiological evidence that the thalamic reticular nucleus comprises part of the thalamic reticular formation: its cellular structure also resembles that of the brain stem regions of the reticular formation (Ramon-Moliner, 1975). Early degeneration and Golgi studies showed that ascending fibres from the medial parts of the pontine and mesencephalic components of the brain stem reticular formation innervated the thalamic reticular nucleus ventrally, by penetrating the zona incerta, and dorsally, via the intralaminar and dorsal thalamic nuclei (Scheibel & Scheibel, 1958). These observations have been confirmed and extended more recently and it appears that the major innervation of the thalamic reticular nucleus occurs via the ventral route which follows the entire course of the reticular nucleus. No fibres ascending from the dorsal column lemniscal system, the spino-cervico-lemniscal system or the spinothalamic tract have been observed to terminate within the thalamic reticular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Response of recticular and dorsal thalamic nuclei neurons during extinction of conditioned implementation in the cat

Unit activity in 66 neurons of the reticular (R) nucleus and 31 neurons of the ventropostrolateral nuclei of the thalamus, and 14 neurons of the posterolateral nuclear complex, the pulvinar, were studied during extinction of the conditioned food implementation reflex. The number of R neurons that had responded to initial excitation in the first 300 msec after the conditional stimulus (CS) decreased with the extinction. Simultaneous disappearance of conditioned-reflex placement movements and late excitatory and inhibitory responses of R and dorsal thalamic nuclei neurons with latent periods exceeding 300 msec was also observed. Extinction of the conditioned reflex (CR) led to a significant lowering of background activity in two-thirds of investigated R and other thalamic nuclear neurons. This suggests that efferent effects from the reticular nucleus are decreased during Cr extinction.

Attempted reversal of cocaine-induced antinociceptive effects with naloxone, an opioid antagonist

We attempted to reverse the behavioral and neuronal antinociceptive effects of cocaine with naloxone, an opioid antagonist. Cocaine (20 mg/kg i.p.) produced a strong analgesic effect in the formalin test and in the tail pinch test. These cocaine-induced analgesic effects could be reversed by naloxone at a very high dose (10 mg/kg) but not at a dose (1 mg/kg) which was sufficient to attenuate morphine (10 mg/kg)-induced analgesia. Naloxone alone at a dose of 10 mg/kg did not produce significant effects. In general, nociceptively evoked responses in medial thalamic neurons were suppressed by cocaine (20 mg/kg), and this suppression was attenuated by naloxone (10 mg/kg). The results suggest that opioid receptors which are not involved in mediating morphine-induced analgesia and which have a low sensitivity to naloxone are involved in cocaine-induced central analgesia.

Saccade-related responses of reticular thalamic neurons in monkey

Saccade-related responses of reticular thalamic neurons in monkey

Ventrolateral and dorsolateral ascending spinal cord pathway influence on thalamic nociception in cat

1. In cat there are two portions of the spinothalamic tract (STT)--a ventral component, the ventral spinothalamic tract (VSTT) made up of axons of cells of spinal cord laminae IV-X, and a dorsolateral component, the dorsolateral spinothalamic tract (DSTT) made up of axons of cells in lamina I of the spinal cord dorsal horn. This study was designed to evaluate thalamic neuronal responses to cutaneous noxious thermal stimuli and to determine the functional importance of pathways ascending in the ventral and dorsolateral portions of the spinal cord, ipsilateral to the thalamic recording site and contralateral to the hindlimb stimulation region, for transmission of nociceptive information to the thalamus. 2. Extracellular single-unit recordings were made from 45 neurons in the ventrobasal complex (VBX) of cat thalamus. Thirty-five of these units responded either exclusively or preferentially to noxious cutaneous stimuli. Responses to noxious thermal stimuli applied to the unit's receptive fields were obtained, and then the effects on these responses of blocking conduction through the dorsolateral funiculus (DLF) and the ventrolateral quadrant (VQ) of the thoracic spinal cord ipsilateral to the thalamic recording site were determined. DLF and VQ conduction blocks were accomplished with the use of a cold probe technique and, at times, surgical lesions of the appropriate portion of the spinal cord. 3. The nociceptive units were located in the periphery of the ventral posterior lateral nucleus (VPL) of the thalamus. Their locations corresponded to the somatotopic organization of VPL. Nociceptive thermal responses were found in both high-threshold (HT) (10 cells) and wide-dynamic-range (WDR) (22 cells) units. The receptive fields of these units were generally small and were located on the hindlimb contralateral to the recording site. The thermoreceptive units had thresholds between 44 and 48 degrees C and were able to code for stimulus intensity. 4. Nine of the 35 nociceptive units demonstrated a decrease in response and two units an increase in response to noxious cutaneous stimulation during DLF block ipsilateral to the recording site and contralateral to the cutaneous stimulation site, whereas four units demonstrated a decrease in response and one unit an increase in response to noxious thermal cutaneous stimulation during VQ block ipsilateral to the recording site and contralateral to the cutaneous stimulation site.(ABSTRACT TRUNCATED AT 400 WORDS)

Thalamic NMDA receptors and nociceptive sensory synaptic transmission

The responses of single thalamic neurones to noxious thermal stimulation were recorded in anaesthetized rats. The selective N- methyl- d-aspartate (NMDA) receptor antagonist, 3-((±)-2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), antagonised nociceptive responses when ejected iontophoretically with currents which produced selective antagonism at NMDA receptors. In contrast, the non-NMDA excitatory amino acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) had little or no effect on nociceptive responses, although it was able to reduce responses to non-nociceptive mechanoreceptor input. These results show that there is substantial NMDA receptor involvement in thalamic nociceptive responses, and that the contribution of CNQX-sensitive non-NMDA receptors to these responses is not extensive. Furthermore, it appears that nociceptive and non-nociceptive input to the thalamus have distinct synaptic pharmacologies.

Thalamic retrograde degeneration following cortical injury: An excitotoxic process?

Traumatic or stroke-like injuries of the cerebral cortex result in the rapid retrograde degeneration of thalamic relay neurons that project to the damaged area. Although this phenomenon has been well documented, neither the basis for the relay neuron's extreme sensitivity to axotomy nor the mechanisms involved in the degenerative process have been clearly identified. Physiological and biochemical studies of the thalamic response to cortical ablation indicate that pathological overexcitation might contribute to the degenerative process. The responses of thalamic projection neurons, protoplasmic astrocytes, and inhibitory thalamic reticular neurons in adult mice were examined from one to 120 days following ablation of the somatosensory cortex as part of an investigation of the role of excitotoxicity in thalamic retrograde degeneration. The responses of thalamic neurons to cortical ablation were compared with those produced by intracortical injection of the convulsant excitotoxin kainic acid, since the degeneration of neurons in connected brain structures distant to the site of kainic acid injection is also thought to occur via an excitotoxic mechanism. Within two days after either type of cortical injury, protoplasmic astrocytes in affected regions of the thalamic ventrobasal complex and the medial division of the posterior thalamic nuclei became reactive and expressed increased levels of immunohistochemically detectable glial fibrillary acidic protein. Within the affected regions of the ventrobasal complex an increased intensity of puncta positive for glutamate decar☐ylase immunoreactivity, presumably due to an increase in its content within the terminals of the reciprocally interconnected thalamic reticular neurons, was also evident. These immunohistochemically detectable alterations in the milieu of the damaged thalamic neurons preceded the disappearance of the affected relay neurons by at least two days following cortical ablation and by seven to 10 days following intracortical kainic acid injection. Regions of the thalamus containing reactive astrocytes corresponded very closely to the regions undergoing retrograde degeneration. Protoplasmic astrocytes in these areas remained intensely reactive up to 60 days after cortical injury. Levels of glutamate decar☐ylase were only transiently elevated in the degenerating regions of the ventrobasal complex following cortical ablation and returned to normal by 14 days. Increased glutamate decar☐ylase immunoreactivity was transiently seen through the entire ventrobasal complex following intracortical kainic acid injection but was markedly more intense in degenerating regions. These patterns of labeling did not return to normal until 50 days after intracortical kainic acid injection, well after the death of the relay neurons. Cortical ablation and intracortical kainic acid injection produce similar alterations in thalamic neuronal and glial populations. The response of thalamic protoplasmic astrocytes to cortical injury may precipitate secondary pathological alterations that directly contribute to the overexcitation of affected relay neurons. Increased activity of inhibitory thalamic reticular neurons may contribute to the degenerative process by paradoxically increasing the excitability of relay neurons in degenerating thalamic regions. These results are consistent with the hypothesis that the thalamic degeneration induced by cortical ablation and intracortical kainic acid injection may share a common excitotoxic mechanism.

Thermal nociceptive responses of VPM thalamic neurons in trained monkeys

Thermal nociceptive responses of VPM thalamic neurons in trained monkeys

Prolonged enhancement of anterior thalamic synaptic responsiveness by stimulation of a brain-stem cholinergic group

This study describes the effects of brain-stem cholinergic laterodorsal tegmental (LDT) stimulation on the synaptic responsiveness of anterior thalamic (AT) neurons. A sample of AT cells, physiologically identified by their short-latency (less than 6.5 msec) response to mammillary body (MB) stimulation, was recorded in unanesthetized, chronically implanted cats and in urethane-anesthetized cats. In chronic experiments, LDT stimulation evoked a short-latency (10-20 msec) excitation in most AT cells. Moreover, brief LDT trains (3 shocks at 300 Hz, every 3 sec) enhanced the responsiveness of AT cells to both MB (orthodromic) and cortical (ortho- and antidromic) stimuli. This effect did not vary as a function of the interval between LDT conditioning and MB or cortical testing shocks, but as a function of the number of trials. The effects of LDT stimuli resisted reserpine treatment (0.75 mg/kg), suggesting that they were not dependent on the coactivation of monoaminergic fibers. Finally, LDT trains did not suppress inhibitory processes in AT neurons when conditioning-testing intervals were longer than 60 msec. Intracellular recordings performed in urethane-anesthetized cats revealed that LDT stimulation induced a short-latency depolarization which increased with membrane hyperpolarization and was associated with an increase in apparent membrane conductance. Usually, isolated LDT trains did not evoke lasting changes in membrane potential or conductance. However, when LDT trains were applied every 3 sec, they gradually decreased the apparent membrane conductance without altering the membrane potential. This conductance change had a time course similar to the LDT-induced potentiation of responsiveness observed in the chronic experiments. In some neurons, LDT conditioning trains also induced a marked increase in the probability of fast prepotentials being triggered by subthreshold MB or cortical orthodromic volleys. In order to distinguish the cumulative effects of repeated LDT trains from the possibly slow time course of LDT influences, we studied the effects of a unique 1 sec LDT train (at 30 Hz) on the synaptic responsiveness of AT cells recorded extracellularly in reserpine-treated, urethane-anesthetized animals. Such LDT trains induced a 2.9-fold increase in synaptic responsiveness, reaching its peak 40-50 sec after the LDT train and lasting up to 4 min. Iontophoretic application of the muscarinic blocker scopolamine blocked these long-lasting potentiating effects of LDT stimuli. Removal of cortical and basal forebrain inputs to the AT nuclear complex by appropriate transections did not abolish the potentiating effects of LDT trains.(ABSTRACT TRUNCATED AT 400 WORDS)

Mapping the Effects of SI Cortex Stimulation on Somatosensory Relay Neurons in the Rat Thalamus: Direct Responses and Afferent Modulation

We have used single-unit recording techniques to map the spatial distribution of the primary somatosensory (SI) cortical influences on thalamic somatosensory relay nuclei in the rat. A total of 193 microelectrode penetrations were made to record single neurons in tracks through the medial and lateral ventroposterior (VPL and VPM), ventrolateral (VL), posterior (Po), and reticular (nRt) thalamic nuclei. Single units were classified according to their (1) location within the nuclei, (2) receptive fields, and (3) response to standardized microstimulation in deep layers of the SI cortical forepaw areas. The SI stimulation produced short-latency (1- to 7-msec) excitatory responses in different percentages of neurons recorded in the following thalamic nuclei: VPL, 42.0%; Po, 25.0%; nRt, 16.4%; VL, 13.6%; and VPM, 9.9%. Within the VPL, the highest proportion of responsive neurons was found in the anterior region. Although most of the VL region was unresponsive, the caudal subregion bordering the rostral VPL showed some responsiveness (13.6% of neurons). In general, the spatial pattern of corticothalamic influences appeared to reciprocate the known thalamocortical connection patterns, but with a heterogeneity that was unpredicted. The same parameters of SI cortical stimulation were used in studies of corticofugal modulation of afferent transmission through the VPL thalamus. A condition-test (C-T) paradigm was implemented in which the cortical stimulation (C) was delivered at a range of time intervals before test (T) mechanical vibratory stimulation was applied to digit 4 of the contralateral forepaw. The time course of cortical effects was analyzed by measuring the averaged evoked unit responses of thalamic neurons to the T stimuli, and plotting them as a function of C-T intervals from 5 to 50 msec. Of the 20 VPL neurons tested during SI stimulation, the average response to T stimulation was decreased a mean of 36%, with the suppression peaking (at 49% inhibition of the afferent response) about 15 msec after the C stimulus. Considerable rostrocaudal variation was observed, however. Whereas neurons in the rostral VPL (near VL) were strongly inhibited (-69%), neurons in the middle and caudal VPL exhibited facilitations at long and short C-T intervals, respectively. This study establishes a specific projection system from the forepaw region of SI cortex to different subregions of the VPL thalamus, producing specific temporal patterns of sensory modulation.