N.A. Buchwald

Caudate intracellular response to thalamic and cortical inputs

Abstract 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.

Intracellular responses of caudate neurons to brain stem stimulation

Abstract Intracellular recordings were made of responses of caudate neurons to stimulation of substantia nigra and adjacent brain stem structures in cats. The locations of brain stem stimulating points which evoked responses in caudate neurons mapped a pathway generally similar to the dopaminergic nigro-striatal tract which was previously described by histochemical means. Lesions in the central median-parafascicular complex of the thalamus did not prevent these nigro-caudate responses from being elicited. Responses in caudate neurons to nigral and supranigral stimuli varied in form, but often included EPSP-IPSP sequences. In such cases the duration of the ‘IPSP’ was always shorter than those evoked in the same neurons by precruciate cortical stimulations or by anterior thalamic stimuli. Effects of stimulus intensity and frequency were assessed. Increases in stimulus intensity increased the amplitude, but not the duration of the intracellular membrane responses. Bursts of high frequency stimulation evoked poststimulus depolarizations of long duration. The possible significance of these long depolarizations for understanding the functions of caudate neurons was discussed.

Intracellular responses of caudate neurons to temporally and spatially combined stimuli

Abstract Intracellular recordings of caudate neuronal responses evoked by temporally combined stimulations of cortex, thalamus, and substantia nigra were made in the cat. Excitatory postsynaptic potentials (EPSPs) which temporally coincided were additive. EPSPs which coincided with an inhibitory postsynaptic potential (IPSP) previously evoked from the same stimulus site were enhanced. The cortical stimulus was prepotent in the sense that EPSPs evoked from thalamic or nigral stimulation were inhibited by the cortical IPSP. The cortical EPSP was enhanced if it was evoked during a nigral or thalamic IPSP. These results are discussed in the context of recent reports concerning the fine structure of synaptic contacts of input fibers to the caudate nucleus.

Intracellular responses of dorsal horn cells to cutaneous and sural nerve A and C fiber stimuli.

Abstract Intracellular recordings were made in 69 L-7 dorsal horn cells in spinal cats. Cells in Rexeds layers IV–VI responding to single shocks to the sural nerve were studied. Three types of short latency (5–10 msec) PSP and spike responses were evoked by low-intensity nerve stimulation: Initial EPSP followed by a long IPSP (31 cells); EPSP only (21 cells); and spikes from baseline only (17 cells). Increasing stimulus intensity to excite both A and C nerve fibers elicited both short-latency and long-latency (> 200 msec) PSP sequences and spikes in 31 cells. Long-latency PSP and spike responses were similar to the shorterlatency responses, but were more frequently followed by spike discharges lasting for several hundred milliseconds. Recruitment of additional spikes per response was sometimes produced by stimulation of C fibers at rates greater than 0.3/sec (“windup”). This phenomenon was related in most cases to a recruitment of additional EPSP per stimulus and was often related to a progressive membrane depolarization. Responses to constant intensity heat were positively accelerating functions of time. These data point to the existence of long-term postsynaptic facilitatory responses activated by small-fiber inputs.

The spontaneous firing pattern of forebrain neurons. I. The effects of dopamine and non-dopamine depleting lesions on caudate unit firing patterns.

Abstract Unilateral lesions in and around the course of the nigrostriatal pathway (in the substantia nigra, in the supranigral region and more rostrally in the area of the medial forebrain bundle) in cats produced a marked slowing of single unit firing in the caudate nucleus contralateral to the lesion. In addition, the medial forebrain bundle lesion produced a tendency for an increase in unit firing rates in the caudate nucleus ipsilateral to the lesion. Lesions in the supranigral region in monkeys produced indications of a slowing in the firing rate of single units in the contralateral caudate and an increase in the firing rate of units in the caudate ipsilateral to the lesion. These alterations in spontaneous unit firing were independent of lesion-induced changes in concentrations of striatal dopamine or the activities of tyrosine hydroxylase and DOPA decarboxylase.

Pallidal and entopeduncular intracellular responses to striatal, cortical, thalamic, and sensory inputs

Abstract Intracellular recordings were made from pallidal and entopeduncular neurons in cats. Responses were evoked by direct brain stimulation and auditory and somatosensory stimuli. Brain sites stimulated were caudate nucleus, the precruciate area of the cerebral cortex, and the central median-parafascicular region of the thalamus. The predominant synaptic response pattern for all types of stimulation was an EPSP-IPSP sequence. Thirty percent of the responses were IPSPs only. Relatively few “pure” EPSPs were recorded. These patterns of synaptic responses were compared with those evoked by comparable stimuli to caudate neurons. In particular, the relatively high percentage of “pure” IPSPs in pallidal and entopeduncular cells contrasted with the rate occurrence of “pure” IPSPs in caudate neurons. This difference in incidence of response types may be attributed to anatomical differences in the fine structure of these nuclei.

Some problems associated with interpretation of physiological and behavioral responses to stimulation of caudate and thalamic nuclei

Abstract Low frequency electrical stimulation of the caudate nucleus or ventral lateral or ventral anterior nucleus of the thalamus inhibits the performance of learned behavior. Concomitant with the behavioral inhibition and elicited by stimuli of the same intensity, is an electrophysiological response consisting of inhibition of unit activity and an associated slow wave which is followed by a spindle. Whether this response is a necessary or sufficient condition for behavioral inhibition has not been fully ascertained, although results of chemical stimulation indicate that behavioral inhibition need not necessarily be accompanied by unit inhibition and spindling. Novel afferent stimulation disinhibits the inhibitory effects of caudate or thalamic stimulation. Under certain conditions, detailed in the text, a disinhibitory stimulus can act as an inhibitor and an inhibitory stimulus can act as a disinhibitor.

Projections to the neostriatum from the cat precruciate cortex. Anatomy and physiology

The projections to the striatum from two cytoarchitectonically and functionally distinct subdivisions of the cat precruciate motor cortex were studied using anatomical and electrophysiological techniques. Our results indicate that the medial precruciate cortex (stimulation of which leads to movements of the axial and proximal musculature) has a widespread projection to the lateral half of the caudate nucleus. The lateral precruciate cortex (stimulation of which leads to movements of the distal musculature) has a localized projection within the caudate nucleus adjacent to the internal capsule. Both medial and lateral precruciate areas project to the putamen. These results are discussed in relation to recent studies suggesting that the basal ganglia are involved in the enabling and sequencing of movements.

The GABAergic striatonigral neurons of the cat: demonstration by double peroxidase labeling.

GABAergic striatonigral neurons were demonstrated in the adult cat by the specific double peroxidase labeling of a transmitter marker with an agranular appearance (GAD, the synthetic enzyme of GABA) and a connectivity marker with a granular appearance (WGA-HRP). Each marker was associated with different organelles confined to the perikaryal cytoplasm of neurons. GABAergic striatonigral neurons were of medium size, high frequency and wide location in the rostral caudate nucleus and putamen based on correlative light and electron microscopic identification. These cells had somatic and/or proximal dendritic spines and folded nuclear envelopes in some cases. They received GABAergic axosomatic and axodendritic inputs with symmetric synaptic specializations. They were also contacted by axosomatic, axodendritic and axospinous terminals with asymmetric synaptic specializations. These results indicate that the GABAergic striatonigral neurons are, for the most part, medium spiny cells that also emit intrastriatal axonal collaterals. Their intra- and extrastriatal axons mediate inhibitory postsynaptic influences on their targets. Their degeneration might contribute to the GABAergic deficits found in the basal ganglia in Huntingtons disease.

Neurophysiological, pharmacological and morphological properties of human caudate neurons recorded in vitro

Tissue samples from the caudate nucleus were obtained from eight children (eight to 172 months of age) who underwent hemispherectomies for the relief of intractable seizures. Neurophysiological, pharmacological and morphological properties of caudate neurons were characterized by intracellular recordings in an in vitro slice preparation. These properties were compared with those of tissue obtained from animal studies. Electrophysiological properties of human caudate neurons that were similar to those of cat caudate and rat neostriatal cells included resting membrane potential, input resistance, action potential rise time, fall time, duration and action potential afterhyperpolarization amplitude, as well as the general characteristics of locally evoked synaptic responses. Properties that were different included action potential amplitudes and time-constants. Human caudate neurons also displayed responses similar to those of cat caudate or rat neostriatal cells to manipulation of excitatory amino acid receptor systems and to dopamine application. Kynurenic acid, a broad-spectrum excitatory amino acid receptor antagonist, decreased the amplitude of evoked synaptic responses, indicating that they were partially mediated by excitatory amino acids. In Mg2+ free Ringers solution, the amplitudes and durations of postsynaptic responses were increased and bursts of action potentials were induced. These effects were mediated by activation of N-methyl-D-aspartate receptors since they were blocked by 2-amino-5-phosphonovalerate, a specific N-methyl-D-aspartate-receptor antagonist. Iontophoretic application of N-methyl-D-aspartate also induced membrane oscillations and bursts in almost all caudate neurons. Dopamine decreased the amplitude of postsynaptic responses, an effect antagonized by domperidone, a selective D2 dopamine receptor antagonist. Developmentally, the greatest change was an increase in action potential amplitude, although input resistance decreased and action potential afterhyperpolarization amplitude increased. Postsynaptic responses were similar across age. All but one of the caudate neurons identified by intracellular injection of biocytin or Lucifer Yellow were medium-sized spiny cells. These experiments show that human caudate neurons display a number of electrophysiological properties similar to rat neostriatal or cat caudate neurons recorded in brain slices. Furthermore, few electrophysiological parameters changed significantly over the age period examined suggesting that the human caudate at eight months displays many of the neuronal functions of the more mature caudate nucleus.