Caudate intracellular response to thalamic and cortical inputs

Intracellular recordings of cat caudate neuronal responses evoked by stimulation of the cerebral cortex or of a number of thalamic sites were made. The predominant response was an EPSP-IPSP sequence. A higher percentage of “pure” EPSPs were recorded from the stimulation of centromedian-parafascicular region than from stimulation of other thalamic sites. The outcomes of these experiments were generally in agreement with recent reports concerning the fine structure of the caudate nucleus. The combined anatomical and physiological data suggest that the great majority of striatal input fibers are excitatory and the majority of interneurons are inhibitory in their synaptic effects.     

Interactions of sensory and nonspecific thalamic inputs to cortical polysensory units in the squirrel monkey

Possible influences of nonspecific thalamocortical projections on sensory responsiveness of single units of polysensory cortex were investigated. Sensory responses in the postarcuate polysensory area (PPA) of the squirrel monkey were paired with antecedent low-frequency (10/sec) trains of stimuli applied to intralaminar nonspecific thalamic nuclei, to elicit recruiting responses indicative of activation of the nonspecific system. Recruiting responses were more prominent in the PPA than primary cortex and, in PPA units, their elicitation typically suppressed the sensory responses with which they were paired, without similarly affecting unpaired inputs to PPA. The reduction in responsiveness persisted for several minutes after the period of pairing in about one-half of the PPA units examined. Primary sensory cortical units were not similarly affected. The data suggest that nonspecific thalamic nuclei project more strongly to polysensory than to primary sensory cortex and that these projections may have the capacity to modulate selectively the responsiveness of polysensory units to peripheral inputs. Possible implications of such plasticity concerning learning are discussed.     

Reticular thalamic responses to nociceptive inputs in anesthetized rats

The present study compares nociceptive responses of neurons in the reticular thalamic nucleus (RT) to those of the ventroposterior lateral nucleus (VPL). Extracellular single-unit activities of cells in the RT and VPL were recorded in anesthetized rats. Only units with identified tactile receptive fields in the forepaw or hindpaw were studied. In the first series of experiments, RT and VPL responses to pinching with a small artery clamp were tested with the rats under pentobarbital, urethane, ketamine, or halothane anesthesia. Under all types of anesthesia, many RT units were inhibited. Second, the specificity of the nociceptive response was tested by pinching and noxious heating of the unit's tactile receptive field. Of the 39 VPL units tested, 20 were excited by both types of noxious stimuli. In sharp contrast, of the 30 RT units tested, none were excited and 17 were inhibited. In a third series of experiments, low-intensity and beam-diffused CO(2) laser irradiation was used to activate peripheral nociceptive afferents. Wide-dynamic-range VPL units responded with short- and long-latency excitations. In contrast, RT units had short-latency excitation followed by long-latency inhibition. Nociceptive input inhibited RT units in less than 500 ms. We conclude that a significant portion of RT neurons were polysynaptically inhibited by nociceptive inputs. Since all the cells tested were excited by light tactile inputs, the somatosensory RT may serve in the role of a modality gate, which modifies (i.e. inhibits) tactile inputs while letting noxious inputs pass.     

Pallidal inputs to subthalamus: Intracellular analysis

Neuronal responses of the subthalamic nucleus (STH) to stimulation of the globus pallidus (GP) and the substantia nigra (SN) were studied by intracellular recording in the decorticated rat. (1) GP and SN stimulation evoked antidromic spikes in STH neurons with a mean latency of 1.2 ms and 1.1 ms, respectively. Based on the above latencies, the mean conduction velocity of the STH neurons projecting toward GP was estimated to be 2.5 m/s, and that toward SN was 1.4 m/s. Many STH neurons could be activated following stimulation of both GP and SN, indicating that single STH neurons project to two diversely distant areas. In spite of differences in conduction distance of GP and SN from STH, differences in the conduction velocities of bifurcating axons make it possible for a simultaneous arrival of impulses in the target areas to which these STH neurons project. (2) GP stimulation evoked short duration (5-24 ms) hyperpolarizing potentials which were usually followed by depolarizing potentials with durations of 10-20 ms. These potentials were tested by intracellular current applications and intracellular injections of chloride ions. The results indicated that the hyper- and depolarizing potentials were IPSPs and EPSPs respectively. These IPSPs were considered to be monosynaptic in nature since changes in the stimulus intensities of GP did not alter the latency of IPSPs. The mean latency of the IPSPs was 1.3 ms. Based on the above mean latency the mean conduction velocity of GP axons projecting to STH was estimated to be 3.8 m/s. (3) Analysis of electrical properties of STH neurons indicated that: (i) input resistance estimated by a current-voltage relationship ranged from 9 to 28 M omega; (ii) the membrane showed rectification in the hyperpolarizing direction; (iii) direct stimulation of neurons by depolarizing current pulses produced repetitive firings with frequencies up to 500 Hz. (4) Morphology of the recorded STH neurons was identified by intracellular labeling of neurons with horseradish peroxidase. Light microscopic analysis indicated that the recorded neurons were Golgi type I neurons with bifurcating axons projecting toward GP and SN.     

Pallidal and entopeduncular single unit activity in cats during drinking.

It has been shown that pallidal units display changes in firing rate during food seeking and consummatory behavior. The purpose of the present work was to determine which properties of the ingested material or ingestive behavior were most potent in altering unit activity. Single unit activity was recorded in the globus pallidus and entopeduncular nucleus of awake restrained cats during introduction of fluid into the mouth. A very high proportion of pallidal and entopeduncular neurons showed changes in firing rate during fluid injection. Two patterns of response were observed. Typically, responses were phasic and time-locked to the occurrence of fluid presentation. Less frequently, a long lasting change in firing occurred which persisted throughout the period of fluid introduction. Additional observations indicated that both of these changes in firing rate seemed to be related to the sensory rather than the motor aspects of ingestion.     

An intracellular analysis of the entopeduncular inputs on the centrum medianum-parafascicular nuclear complex in cats

Intracellular recording from the CM-PF neurons was performed by stimulation of the EN, the caudate nucleus (Cd), the cerebellar nuclei (CN) and the motor cortex in the cat under Nembutal anesthesia. Twenty-seven neurons in the CM-PF nuclear complex and two neurons near the habenular nucleus received monosynaptic inhibitory postsynaptic potentials (IPSPs; latency of 1.0–4.0 ms, mean 2.3 ms) by EN stimulation. Cd stimulation evoked excitatory postsynaptic potentials (EPSPs) followed by long hyperpolarizations in most of the CM-PF neurons and produced antidromic activation in 7 neurons. Six neurons received EPSPs (latencies of 4–7 ms) by cortical stimulation. CN stimulation affected only two neurons in the present study. Intracellular HRP staining revealed that some CM-PF neurons have polygonal or spindle-shaped somata with fine, long and sparsely spinous dendrites.     

Long latency responses in pure sensory stroke due to thalamic infarction

Objectives – Our study was designed to clarify the role of the thalamus in the generation of the electrically elicited long-latency reflexes (LLR) in voluntarily activated hand muscles. Materials and methods – EMG responses of the thenar muscles were evoked by electrical stimulation of the median nerve at the wrist at motor threshold intensity in 10 patients with acute pure sensory stroke due to thalamic infarction. Concomitant recording of somatosensory evoked potentials (SEPs) was performed. The subjects were asked to steadily abduct the thumb at 20–30% of maximal force against a force transducer. Rectified and averaged EMG activities were recorded. Results – The LLR II was missing completely or significantly attenuated in the majority of the patients (9 of 10), of whom 3 also had delayed latency. Abnormal SEPs were documented in 7 patients (7 of 10). In the follow-up, 5 patients had partial reversal of LLR II. LLR II was still pathological in 1 fully recovered patient. Conclusion – Our results further confirm the transcortical generation of LLR II and imply that a thalamic relay is present in the afferent limb of the LLR.     

Pallidal and thalamic neurostimulation in severe tardive dystonia

A 70 year old woman presented with a 6 year history of medically refractory severe tardive dystonia. After informed consent, a bilateral stereotactic electrode placement targeting the ventral intermediate thalamic nucleus (VIM) and the globus pallidus internus (GPi) was performed. After bilateral stimulation of the GPi, the patient showed a clear and stable improvement of the painful dystonic syndrome within hours. Stimulation of the VIM did not improve the hyperkinetic movements and simultaneous stimulation of both the GPi and the VIM did not result in any additional benefit. The possible pathophysiological mechanisms are discussed.     

Functional and molecular development of striatal fast-spiking GABAergic interneurons and their cortical inputs

Despite their small number, fast-spiking (FS) GABAergic interneurons play a critical role in controlling striatal output by mediating cortical feed-forward inhibition of striatal medium-sized spiny (MS) projection neurons. We have examined the functional development of FS interneurons and their cortical inputs, and the expression of three of their molecular markers, in the dorsolateral rat striatum between postnatal days (P)12--14 and 19--23, the time of major corticostriatal synaptogenesis. FS interneurons were visualized with infrared differential interference contrast (IR-DIC) optics and examined with current-clamp recording in the presence of the GABA(A) receptor antagonist bicuculline methiodide. FS interneurons displayed action potentials at relatively high frequencies in response to depolarizing current pulses by P12, but developmental changes occurred in action potential and afterhyperpolarization duration and amplitude and input resistance between P12--14 and P19--23, as well as an increase in maximum firing frequency in response to depolarizing current pulses. Maturation in electrophysiological properties was paralleled by increases in Kv 3.1 and parvalbumin mRNA expression, while GAD-67 mRNA levels remained constant. Furthermore, FS interneurons in the younger age group responded to stimulation of cortical afferents with excitatory postsynaptic potentials (EPSPs) of higher amplitudes and received significantly more spontaneous depolarizing inputs than did MS neurons. Thus, FS interneurons are under frequent and continuous cortical influence by the end of the 2nd postnatal week, a time when corticostriatal synapses are sparse, suggesting that they may provide a major inhibitory influence in the striatum during the period of intense developmental maturation.     

Ipsilateral trigeminal sensory responses to cortical stimulation by subdural electrodes

Twelve patients with medically intractable epilepsy had plates of chronic subdural electrodes placed over the lateral and basal cortical hemispheres during evaluations for surgical therapy. During cortical stimulation, ipsilateral sensations involving any of the branches of the trigeminal nerve were noted in the eye, face, and mouth. Some responses could have been due to dural or direct trigeminal nerve trunk stimulation, but others were probably due to electrical stimulation of trigeminal fibers accompanying the pial-arachnoidal vessels. These fibers had been demonstrated in animals, but not in humans.     

Long-term potentiation in freely moving rats reveals asymmetries in thalamic and cortical inputs to the lateral amygdala

Long-term memory underlying Pavlovian fear conditioning is believed to involve plasticity at sensory input synapses in the lateral nucleus of the amygdala (LA). A useful physiological model for studying synaptic plasticity is long-term potentiation (LTP). LTP in the LA has been studied only in vitro or in anaesthetized rats. Here, we tested whether LTP can be induced in auditory input pathways to the LA in awake rats, and if so, whether it persists over days. In chronically implanted rats, extracellular field potentials evoked in the LA by stimulation of the auditory thalamus and the auditory association cortex, using test simulations and input/output (I/O) curves, were compared in the same animals after tetanization of either pathway alone or after combined tetanization. For both pathways, LTP was input-specific and long lasting. LTP at cortical inputs exhibited the largest change at early time points (24 h) but faded within 3 days. In contrast, LTP at thalamic inputs, though smaller initially than cortical LTP, remained stable until at least 6 days. Comparisons of I/O curves indicated that the two pathways may rely on different mechanisms for the maintenance of LTP and may benefit differently from their coactivation. This is the first report of LTP at sensory inputs to the LA in awake animals. The results reveal important characteristics of synaptic plasticity in neuronal circuits of fear memory that could not have been revealed with in vitro preparations, and suggest a differential role of thalamic and cortical auditory afferents in long-term memory of fear conditioning.     

Thalamic innervation of striatal and subthalamic neurons projecting to the rat entopeduncular nucleus

The present study analyses the anatomical arrangement of the projections linking the Wistar rat parafascicular thalamic nucleus (PF) and basal ganglia structures, such as the striatum and the subthalamic nucleus (STN), by using neuroanatomical tract-tracing techniques. Both the thalamostriatal and the striato-entopeduncular projections were topographically organized, and several areas of overlap between identified circuits were noticed, sustaining the existence of up to three separated channels within the Nauta-Mehler loop. Thalamic afferents arising from dorsolateral PF territories are in register with striatofugal neurons located in dorsolateral striatal areas, which in turn project to dorsolateral regions of the entopeduncular nucleus (ENT). Medial ENT regions are innervated by striatal neurons located within medial striatal territories, these neurons being the target for thalamic afferents coming from medial PF areas. Finally, afferents from neurons located in ventrolateral PF areas approached striatal neurons in ventral and lateral striatal territories, which in turn project towards ventral and lateral ENT regions. Efferent STN neurons projecting to ENT were found to be the apparent postsynaptic target for thalamo-subthalamic axons. The thalamo-subthalamic projection was also topographically organized. Medial, central and lateral STN territories are innervated by thalamic neurons located within medial, ventrolateral and dorsolateral PF areas, respectively. Thus, each individual PF subregion projects in a segregated fashion to specific parts of the striato-entopeduncular and subthalamo-entopeduncular systems. These circuits enabled the caudal intralaminar nuclei to modulate basal ganglia output.     

Influence of thalamic cooling on sensory responses in association cortex

O'BRIEN, J. H. AND S. M. ROSENBLUM. Influence of thalamic cooling on sensory responses in association cortex. BRAIN RES. BULL. 4(1) 91–98, 1979.—Evoked responses to light flash, click, and paw stimuli were recorded in the four cortical association areas in the acutely prepared cat. Average evoked responses (AEP) for 100 trials were formed before, during, and after localized cooling in the midline thalamus. Cooling of the midline thalamus reduced the magnitude of responses to click and paw stimuli, and increased or did not change the responses to light flash. There was very little similarity in trial-to-trial fluctuations of EP magnitude across cortical areas, and cooling did not reduce the similarity that existed. Waveform similarity was reduced by cooling for responses across the cortex to a single stimulus modality, whereas similarity of responses in a single cortical area to all three stimuli was not changed. The temporal components of the AEP influenced by thalamic cooling were different for different stimuli and cortical locations. It was concluded that the midline thalamo-cortical projection through the centromedian area to association cortices is particularly well-differentiated for multisensory responses in a single cortical region, and that the system should not be thought of as nonspecific but as convergent or multisensory.     

Synaptic organization and input-specific short-term plasticity in anterior cingulate cortical neurons with intact thalamic inputs

The absence of a slice preparation with intact thalamocortical pathways has held back elucidation of the cellular and synaptic mechanisms by which thalamic signals are differentially transmitted to and processed in the anterior cingulate cortex (ACC). In this report we introduce an innovative mouse brain slice preparation in which it is possible to explore the electrophysiological properties of ACC neurons with intact long-distance inputs from medial thalamic (MT) nuclei by intracellular recordings; this MT-ACC neuronal pathway plays an integral role in information transmission. Biocytin-labeled fibers in a functional slice could be traced anterogradely or retrogradely from the MT via the reticular thalamic nuclei, striatum and corpus callosum to the cingulate cortical areas. Eighty-seven cells downstream of the thalamic projections in 49 slices were recorded intracellularly. Intracellular recordings in the ACC showed that thalamocingulate transmission involves both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors. Thalamus-evoked responses recorded extracellularly in the ACC were activated and progressed along a deep-superficial-deep trajectory loop across the ACC layers. We observed enhanced paired-pulse facilitation and tetanic potentiation of thalamocingulate synapses, suggestive of input-specific ACC plasticity and selective processing of information relayed by thalamocingulate pathways. Furthermore, we observed differential responses of ACC neurons to thalamic burst stimulation, which underscores the importance of MT afferents in relaying sensory information to the ACC. This new slice preparation enables the contribution of MT-evoked ACC synaptic transmission to short-term plasticity in the neuronal circuitry underlying sensory information processing to be examined in detail.     

Maturation of thalamic inputs into the associative cortical areas during postnatal ontogenesis in cats

Thalamic afferents into the sensorimotor and parietal cortex (area 7) were studied using the method of retrograde axonal transport of horseradish peroxidase (HRP) in kittens of three age groups. Following HRP injection into the sensorimotor cortex of 1- to 3-day-old kittens, labeled cells were found in the following nuclei: ventral posterolateral (VPL), ventral posteromedial (VPM), medialis dorsalis (MD), centrum medianum (CM), ventral posteromedial (VPM), medialis dorsalis (MD), centrum medianum (CM), and centralis lateralis (CL). In 9- to 10-day-old kittens the number of labeled cells and density of reaction product within the cells was found to increse markedly. In 21- to 30-day-old kittens, besides the above-mentioned nuclei, labeled cells were also revealed in n. ventralis lateralis (VL). A similar trend was seen following HRP injections into area 7. In 1- to 3-day-old kittens, labeled cells were found in n. lateralis posterior (LP), in n. ventralis anterior (VA), and in Pulvinar (Pulv). Both in the 9-to 10-day-old and the 21- to 30-day-old kittens, labeled cells were also demonstrated in n. lateralis dorsalis (LD) and CL. For both of the cortical areas the number of labeled cells and the density of labeling within the cells increase during postnatal ontogenesis. This may be attributed to the growing number of axon terminals. In general, our results suggest that differences in the thalamic connections of single cortical areas can be distinguished during the postnatal ontogenesis of the brain.     

Role of the entopeduncular nucleus in caudate nucleus-induced suppression of intralaminar thalamic unit responses in the cat

Suppression by caudate nucleus stimulation of nonspecific sensory responses in the intralaminar thalamus could potentially be mediated by either of two major pathways, through the entopeduncular nucleus or through the pars reticulata of the substantia nigra. The role of the entopeduncular nucleus was investigated in the chloralose-anesthetized cat by (i) comparison of the effects of conditioning stimuli, applied to either the entopeduncular nucleus or the caudate nucleus, on somatic-evoked single-unit responses in the intralaminar thalamus and (ii) acute interruption of caudate nucleus outflow pathways. Entopeduncular stimulation duplicated caudate-induced suppression of intralaminar responses, invariably at lower stimulus thresholds, and, unlike caudate stimulation, often evoked excitatory responses preceding suppression. Lesions of the entopeduncular nucleus greatly attenuated caudate-induced suppression, whereas selective interruption of the caudatonigral pathway had no significant effect. Thus, caudate-induced suppression of intralaminar responses is mediated primarily by the entopeduncular nucleus and may involve activation of entopeduncular efferent fibers which directly or indirectly inhibit intralaminar neurones. These findings suggest that differential behavioral functions may be subserved by caudate outflows through the entopeduncular nucleus and substantia nigra.     

A model that accounts for activity prior to sensory inputs and responses during matching-to-sample tasks

Neural network models were examined during delayed matching-to-sample tasks (DMS), and neurons in a monkey's prefrontal cortex were studied during the performance of comparable tasks. In DMS, various input stimuli follow a sample stimulus, and an output should occur whenever the sample reappears. Our previous models have been restricted to certain kinds of inputs, outputs, and temporal patterns. Here, we generalized the models by training them on both spatial and nonspatial inputs, spatial and nonspatial outputs, and both fixed and variable interstimulus intervals. Two versions of DMS were presented to both the model and the monkey, both involving nonspatial samples: (1) Two stimuli simultaneously appeared at a variable interval after the sample; and (2) A series of single stimuli appeared at fixed intervals after the sample. Both versions required identical spatial responses, reflecting the direction (left or right) of the matching stimulus relative to a central origin. Thus, these two versions of DMS involved the same samples, memory, and responses, but established different response contexts. Our analysis focused on unit activity prior to stimuli, as well as that prior to responses, termed anticipatory and response-related activity, respectively. In both the model and the monkey, anticipatory activity occurred only for fixed interstimulus intervals. In the model, we could determine that anticipatory activity acted either like a filter to suppress inappropriate responses or it served to enhance the network's general readiness to respond. As for response-related activity, units in both the model and the monkey showed directional selectivity and had a strong dependence on response context. In the model, we could show that this activity contributed both to the suppression of inappropriate responses and to the generation of correct ones. None of the model's hidden units contributed exclusively to computing the direction of match output. Instead, their response-related activity contributed to the computation of both the match decision and the correct response direction.