Caudal Neurons Research Articles

Electroconvulsive shock decreases excitatory responses to serotonin in the caudate nucleus of the rat

Contreras Carlos M., Guillermo Sánchez Estrada, Miguel Molina Hernández and Ma. Luisa Marván. Electroconvulsive shock decreases excitatory responses to serotonin in the caudate nucleus of the rat. Prog. Neuro-Psychopharmacol & Biol Psychiat. 1994, 18(1): 193–199. 1. 1. The present study explored the changes on the firing rate of caudate neurons, and the response to serotonin locally applied in rats submitted to electroconvulsive shock. 2. 2. Electroconvulsive shock diminished the firing rate of caudate neurons and blocked the excitatory response produced by serotonin in a small amount of serotonin-sensitive neurons. 3. 3. Results are likely to be related with transient changes in the receptor's affinity and dissociation constants, which may impinge on immediate memory retrieval.

Responses of feline caudal hypothalamic cardiorespiratory neurons to hypoxia and hypercapnia.

Several studies have suggested that the caudal hypothalamus modulates responses to hypercapnia and hypoxia. In addition, this area of the hypothalamus contains neurons that have a sympathoexcitatory discharge. The purpose of the present study was to determine whether the basal discharge of caudal hypothalamic neurons that are stimulated by hypercapnia or hypoxia is related to cardiovascular (sympathetic discharge and/or the cardiac cycle) and/or respiratory activity (phrenic nerve discharge). Hypothalamic single unit activity, phrenic nerve activity, and cervical sympathetic nerve activity were recorded in anesthetized cats. Computer averaging techniques were used to compare temporally the discharge of hypothalamic neurons with cardiovascular and/or respiratory activity. Cardiorespiratory and hypothalamic neuronal responses to ventilation with hypoxic (10% O2/90% N2) and hypercapnic (5% CO2/95% O2) gases were determined in intact and in peripherally-chemodenervated, barodenervated cats. Thirty-two percent of hypothalamic neurons were stimulated by a hypercapnic stimulus in intact cats; of those that were stimulated by hypercapnia, all had a basal discharge related to cardiovascular and/or respiratory activity. Hypoxia significantly increased the discharge rate of 21% of hypothalamic units in intact animals; 90% of those had a cardiovascular and/or respiratory-related rhythm. Only 13% of the neurons were stimulated by both hypoxia and hypercapnia. Similar results were found in barodenervated, peripherally chemodenervated cats. Neurons excited by these stimuli in both the intact and denervated cats were found to be concentrated in the posterior hypothalamic area. The results of this study suggest that a group of caudal hypothalamic neurons contribute to the cardiorespiratory responses to hypoxia and hypercapnia, but via separate subpopulations of neurons. In addition, input from peripheral baroreceptor and chemoreceptor afferents is not required for this modulation.

Response of caudate neurons to stimulation of intrinsic and peripheral afferents in normal, symptomatic, and recovered MPTP-treated cats

Cat caudate nucleus (CD) neurons were tested for changes in spontaneous activity, response to peripheral sensory stimuli (tactile, auditory, and visual), and electrical stimulation of monosynaptic afferents (pericruciate cortex and nucleus centralis lateralis) in normal cats and in the same cats after induction of and spontaneous recovery from parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After normal baseline data were collected, cats were given MPTP (7.5 mg/kg, 5-7 d) to induce a parkinsonian syndrome consisting of rigidity, akinesia, and decreased orienting to sensory stimuli. During this symptomatic period, the mean spontaneous activity of CD units increased (6.20 spikes/sec vs 2.25 spikes/sec in normal cats). In these same animals, the percentage of units responding to peripheral sensory stimulation was significantly decreased (compared to normal) while the percentage of units responding to electrical stimulation of monosynaptic afferents increased. By 6 weeks after MPTP administration, cats had recovered gross motor and sensorimotor function and CD unit recordings were reinitiated. In functionally recovered animals, all electrophysiological measures returned to levels resembling those seen in normal animals. These data suggest that the processing of peripheral sensory information is an important part of basal ganglia function and that the sensory responsiveness of the CD may reflect the overall motor condition of the animal. The changes observed in the responsiveness of CD neurons to direct electrical stimulation of monosynaptic afferents may indicate that the defect in the processing of polysynaptic sensory information observed in the striatum in parkinsonian animals may be occurring, at least in part, extrastriatally.

No evidence for presynaptic opioid receptors on cholinergic, but presence of ?-receptors on dopaminergic neurons in the rabbit caudate nucleus: involvement of endogeneous opioids

The effects of various opioid receptor agonists and antagonists were studied in rabbit caudate nucleus slices preincubated with either [3H]dopamine or [3H]choline, superfused with medium (containing in most experiments the D2 receptor antagonist domperidone) and subjected to electrical field stimulation. The stimulation-evoked [3H]overflow from slices prelabeled with [3H]dopamine (evoked [3H]dopamine release) was significantly reduced by preferential kappa-opioid receptor agonists, like U-50,488 H, but not by mu- or delta-opioid receptor selective drugs. Opioid receptor antagonists shifted the concentration/response curve of U-50,488 H to the right (apparent pA2-value of the kappa-selective antagonist nor-binaltorphimine: 10.1) and enhanced the evoked dopamine release in the presence of a mixture of peptidase inhibitors. On the other hand, the [3H]overflow from rabbit caudate nucleus slices prelabeled with [3H]choline (evoked acetylcholine release) remained almost unaffected by any opioid receptor agonist, as long as the presynaptic D2 heteroreceptor was blocked with domperidone: in the absence of domperidone, U-50,488 H exhibited facilitatory effects. For comparison, the effects of the preferential delta-opioid receptor agonist DPDPE was also studied in slices of the rat striatum, where it clearly inhibited the evoked acetylcholine release. From our data we conclude that in the rabbit caudate nucleus the evoked dopamine release is inhibited by both exogenous and endogenous opioids via presynaptic kappa-opioid receptors, whereas the evoked release of acetylcholine is not, or only indirectly (via released dopamine) affected by opioids.

Nucleus ambiguus of the rabbit: cytoarchitectural subdivision and myotopical and neurotopic representations.

The cytoarchitectural subdivisions of the nucleus ambiguus of the rabbit and its myotopical and neurotopical representations were investigated with HRP labeling. The nucleus was subdivided into the compact cell group (CoG), the medial and lateral scattered cell groups (SGm and SGl), and the diffuse cell group (DiG). The CoG was formed by esophageal, pharyngeal constrictor, and palatal motoneurons in the rostral half of the nucleus. The SGm and SGl were located medial and lateral to the CoG, respectively, in the rostral one-third of the nucleus. Stylopharyngeal and cricothyroid motoneurons were located in the most rostral one-fifth of the SGm and the remaining four-fifths, respectively, whereas the SGl was not labeled with HRP injections into the palatal, pharyngeal, esophageal, and laryngeal muscles. The DiG was formed by recurrent laryngeal motoneurons in the caudal two-thirds of the nucleus. Neurons of origin for the glossopharyngeal nerve occupied the stylopharyngeal region, with a few of them scattered in the CoG and SGl. Neurons giving rise to axons in the superior laryngeal nerve occupied the cricothyroid region, with a few of them scattered in the pharyngeal constrictor region; whereas the pharyngeal vagal branch originated from the pharyngeal constrictor and palatal regions. Neurons of the DiG, SGl, and esophageal region contributed to the infranodosal vagus nerve; esophageal fibers of the recurrent laryngeal nerve originated from the dorsal esophageal region. Laryngeal fibers of the recurrent laryngeal nerve originated from the DiG, the caudal neurons of which had axons traversing the cranial accessory root.

Physiological and developmental aspects of intersegmental coordination in Xenopus embryos and tadpoles

The rostro-caudal delay in the activation of the segmentally organised trunk muscles is a consistent feature of forward swimming in the tadpoles of Xenopus laevis. Our evidence suggests that such a delay may be achieved because rostral neurons are associated with a higher level of excitability than caudal neurons and so fire first on cycles of swimming. In addition we have found developmentally related changes in the properties of rostro-caudal delays in Xenopus, whereby the duration of motor nerve activity increases, a constant phaselag becomes established and there is increased sensitivity to 5-HT. These changes may be directly related to the incorporation of descending serotonergic neurones into the spinal cord network, so providing a means of determining the role played by identifiable neural elements in intersegmental coordination in the Xenopus preparation.

Effect of irradiation by semiconductor laser on responses evoked in trigeminal caudal neurons by tooth pulp stimulation.

The effect of irradiation with a gallium-aluminum-arsenide semiconductor laser on responses evoked in trigeminal subnucleus caudal neurons by tooth pulp stimulation was investigated electrophysiologically in Wistar rats anesthetized with urethane plus alpha-chloralose. The pulp of lower incisor was electrically stimulated and the evoked action potentials were extracellularly recorded in the ipsilateral caudal neurons. The laser beam was applied on the cervical surface of the stimulated incisor. The rate of firing discharges and the numbers of spikes evoked in the caudal neurons were compared before and after laser irradiation. Laser irradiation suppressed the late discharges in the response of the caudal neurons which were evoked by excitatory inputs from C-fiber afferents, but did not suppress the early discharges evoked by inputs from A delta-fiber afferents. This indicates that low power laser irradiation (semiconductor laser: 830 nm, 350 mW, CW, through the tooth structures, for 120 s) inhibited the excitation of unmyelinated fibers of the pulp without affecting fine myelinated fibers. These results suggest that low power laser irradiation has a suppressive effect on injured tissue by blocking the depolarization of C-fiber afferents.

Fos family member changes in nucleus caudalis neurons after primary afferent stimulation: enhancement of fos B and c- fos

In situ hybridization using cDNAs complementary to specific regions of the mRNAs encoding four members of the FOS transcription factor gene family reveals modest levels of hybridization over superficial lamina of the nucleus caudalis of the spinal tract of the trigeminal in sections taken from unstimulated brains. Fos B expression is markedly and rapidly enhanced ipsilateral to electrical stimulation of the trigeminal ganglia. c= fos mRNA also changes; these differences contrast with the lack of significant changes in the low basal levels of expression of fra-1 and fra-2 mRNAs. The prominent change in fos B mRNA is mediated largely by an increase in the number of neurons that express hybridization densities above background after stimulation. This result, taken together with data on stimulation-induced changes in expression of preproenkephalin and other AP-1 transcription factors in wild-type animals and stimulation-induced changes in CAT activity in transgenic mice expressing portions of the proenkephalin promoter, is consistent with a role for the enhanced fos B expression in upregulation of expression of preproenkephalin in these neurons.

Fourth ventricular injection of selective bombesin receptor antagonists facilitates feeding in rats

Exogenous bombesin (BN)-like peptides exert their effects on feeding through caudal brain stem BN-like peptides and their receptors. To determine if endogenous BN-like peptides are involved in the control of feeding and exert their actions on caudal brain stem neurons, nondeprived rats were administered fourth ventricular injections of either saline or BN receptor antagonists in the following doses: 5 and 25 ng [D-Phe12,Leu14]BN or 5 ng [D-Phe6]BN(6-13)methyl ester. Milk intake was measured every 5 min and each animal's behavior (eating, grooming, exploring, resting) was monitored every 1 min for 60 min. Compared with saline injections, fourth ventricular injections of 25 ng [D-Phe12,Leu14]BN and 5 ng [D-Phe6]BN(6-13)methyl ester reliably facilitated milk intake. The enhanced milk intake was evident within 5 min after the injection and persisted throughout the 1-h intake test. The behavioral sequence following fourth ventricular injections of saline and the antagonists that facilitated feeding were similar. Injections of [D-Phe12,Leu14]BN and [D-Phe6]BN(6-13)methyl ester did not produce a generalized arousal. The results indicate that food-contingent, endogenous BN-like peptides contribute to the termination of feeding and exert their behavior-controlling actions on BN-like peptide receptors in the vicinity of the fourth ventricle.

Wind-up of tooth pulp-evoked responses and its suppression in rat trigeminal caudal neurons

Induction and suppression of wind-up were studied in 97 tooth pulp-driven neurons in the trigeminal subnucleus caudalis, using Wistar albino rats anesthetized with urethane and alpha-chloralose. Tooth pulp stimulation applied to an ipsilateral lower incisor evoked early discharges, indicating excitatory inputs from A-delta fibers and subsequent late discharges from C-fiber volleys in caudal neurons. Wind-up was efficiently evoked by stimulation delivered at 0.3–1 Hz, with current intensity sufficient to evoke late discharges. Conditioning stimulation of the arcuate nucleus of the hypothalamus (ARH) suppressed late discharges, including wind-up, without affecting the A-fiber response. Focal cooling of the periaqueductal gray (PAG) abolished the suppression by the ARH and further enhanced the wind-up of the caudal neurons. These results suggest: 1. 1) Temporal summation of depolarization evoked by C-fiber volleys builds wind-up in caudal neurons; 2. 2) ARH stimulation suppresses late discharges by blocking synaptic transmission from C-fiber inputs, and this interrupts prolonged facilitation of the neurons; 3. 3) the ARH is involved in induction of inhibitory controls descending from the PAG to the trigeminal caudalis.

Striatal neuronal activity during the initiation and execution of hand movements made in response to visual and vibratory cues.

Recordings were obtained from 146 neurons in the neostriatum of rhesus monkeys while they performed wrist movements in response to visual and vibratory cues. Of these, 75 putamena nd 29 caudate neurons exhibited changes in firing rate that were temporally related to the onset of the wrist movements and that began prior to movement onset. This premovement activity (PMA) usually was directionally specific, in that the magnitude or direction of change in firing rates was different during flexion trials as compared to trials involving wrist extension. PMA onset usually preceded movement onset by more than 100 ms and in most instances preceded the average onset of task-related changes in electromyographic (EMG) activity in muscles of the wrist and forelimb. For most neurons, the changes in neuronal activity that began prior to movement were maintained during movement execution. However, approximately one-third of the neurons that exhibited PMA changed their firing rate in the opposite direction, relative to their PMA and to their baseline rate of activity, once the movement began. Several other neurons either exhibited PMA only or they altered their discharge rates during movement execution but did not exhibit PMA. These observations suggest that, despite the close temporal relationship between the onset of PMA and the onset of wrist movement, the neuronal mechanisms mediating the PMA may differ from those that occur during movement execution. The PMA onset of neostriatal neurons occurred earlier in visually cued than in vibratory cued trials. These differences were statistically significant only for flexion trials, however, in which movements were made against a load and in the same direction as the palmar vibratory stimulus. For trials involving wrist extension, PMA onsets for visually cued as compared with vibratory cued trials were not statistically different. These findings contrast with data obtained previously from somatosensory cortical neurons during performance of the same behavioral task. On average, PMA in the putamen began earlier, relative to movement onset, than it did in the somatosensory cortex. Moreover, in the somatosensory cortex, PMA onset occurred earlier in vibratory cued than in visually cued trials, irrespective of movement direction (Nelson 1988; Nelson and Douglas 1989). For putamen neurons, but not for caudate or cortical neurons, the onset of PMA also occurred significantly earlier during extension trials than flexion trials, irrespective of the modality of the "go-cue".(ABSTRACT TRUNCATED AT 400 WORDS)

Serotonin-like immunoreactivity in the ventral nerve cord of the Colorado potato beetle, Leptinotarsa decemlineata: Identification of five different neuron classes

In an immunohistochemical study of the ventral nerve cord of L. decemlineata, five distinct neuron categories were distinguished: 1) Two paired segmental twin interneurons occur in each ganglion or neuromere; their axons distribute processes over almost the entire nerve cord and run to the cerebral ganglion complex. In contrast, other axons are distributed locally. 2) Four large frontal neurosecretory neurons occur in the suboesophageal ganglion (SOG), two of which have axons that run into the mandibular nerves to form a neurohemal plexus on the surface of cerebral nerves. 3) A pair of large caudal neurons occur in the terminal ganglion and innervate the hindgut. 4) Local miniature interneurons occur in the SOG. 5) Terminal neurons are present in the last abdominal ganglion. Segmental twin interneurons appear to be grouped into 3 ‘functional units’ spanning several ganglia. Their axons run to specific projection areas, which separate the functional units, and which mark the externally visible separation of condensed ganglion complexes. A possible role of the most caudal functional unit might be the synaptic control of caudal neurons innervating the hindgut.

Expression of Fos-like proteins in gonadotropin-releasing hormone neurons of Syrian hamsters: effects of estrous cycles and metabolic fuels.

In female mammals, reproduction is sensitive to the availability of metabolic fuels, and food deprivation has been shown to suppress pulsatile LH secretion, attenuate the preovulatory LH surge, and prevent ovulation. It has been suggested that food deprivation impairs fertility by reducing the secretion of GnRH by GnRH-producing neurons in the forebrain. A series of experiments tested this hypothesis by examining the effects of estrous cycles and manipulations of metabolic fuel availability on the expression of Fos-like proteins (Fos-IR) in GnRH-immunoreactive (GnRH-IR) neurons in the forebrain of Syrian hamsters. GnRH-IR neurons were detected in several areas, including the diagonal band of Broca (DBB), medial septum (MS), rostral medial preoptic area (mPOA), and caudal POA. In the more rostral regions (DBB and MS/mPOA), GnRH-IR neurons expressed Fos-IR almost exclusively on day 4 of the cycle, just after the preovulatory LH surge. However, in the caudal POA, GnRH-IR neurons expressed Fos-IR across the entire cycle, including days 1-3, when LH secretion is pulsatile. Food deprivation on days 1 and 2 of the cycle, which attenuates the LH surge and blocks ovulation in hamsters, significantly reduced the proportion of GnRH-IR neurons that expressed Fos-IR on days 2 and 4 (caudal POA) or only on day 4 (DBB and MS/mPOA). Suppression of fuel availability with insulin or 2-deoxy-D-glucose on day 1 of the cycle mimicked the effects of food deprivation and reduced the proportion of caudal POA GnRH-IR neurons that expressed Fos-IR. The results of these experiments suggest that in Syrian hamsters, there are separate populations of GnRH-IR neurons associated with pulsatile and surge modes of LH secretion. In addition, the fact that manipulations of metabolic fuel availability cause changes in the expression of Fos-IR in both populations of GnRH-IR neurons provides strong support for the hypothesis that nutritional infertility is due in part to decreased GnRH secretion.

Spontaneous and evoked activity of the caudate neurons to central and peripheral stimuli after brain lesions

The involvement of the cerebral cortex, commissural fibers and thalamus on caudate-caudate relations was studied in locally anesthetized, paralysed and artificially ventilated cats. This type of experimental preparation was necessary since a complete suppression of spontaneous and evoked activity is produced by subanesthetic doses of general anesthesia. Two types of caudate action potentials were encountered on the basis of their waveform characteristics: biphasic and triphasic spikes, the former being the largest population (80%). These waveforms were independent of the microelectrode resistance and the distance to recorded neurons. However, their responses were very similar to both central and peripheral stimuli. Caudate stimulation depressed the spontaneous discharges of the majority of the responsive units recorded within the opposite nucleus, while striatal neurons were activated by stimulation of the contralateral cortex. Decortication, thalamic lesion (motor nuclei and massa intermedia) and section of the corpus callosum decrease the firing rates of caudate neurons with biphasic spikes, while the discharges of the neurons with triphasic action potentials remained unchanged. Bilateral ablation of the cerebral cortex decreased the responsiveness of striatal neurons to contralateral nucleus and sciatic nerve and reduced the number of spontaneously active cells per recording tract. Section of the commissural fibers also depressed the caudate responses to the contralateral nucleus and to the opposite precruciate cortex, although thalamic lesion did not affect the responsiveness of caudate cells to both central and peripheral stimuli. Taking into account the present data and those from a previous paper [O'Donnell P. et al. (1989) Neuroscience 33, 543–548], we concluded that there is a functional relationship between both caudate nuclei, which is partially mediated by the corpus callosum.

A topographic representation of auditory space in the external nucleus of the inferior colliculus of the guinea-pig

The possibility that the external nucleus of the inferior colliculus (ICX) of the pigmented guinea-pig contains a map of auditory space has been investigated. Auditory stimuli consisted of broad-band sound delivered under free-field anechoic conditions from a range of positions around the animal's azimuthal axis. The responses of clusters of neurons in the ICX to threshold and to near-threshold stimuli displayed sharp spatial tuning. The responses recorded from rostral ICX revealed a preference for auditory stimuli in the anterior field while more caudal neurons preferentially responded to sounds presented in the posterior field. Neurons at intermediate points, along the rostro-caudal axis of the nucleus, displayed preferences for sound stimuli in appropriately intermediate field positions along the contralateral azimuthal axis. At higher stimulus intensities the spatial tuning of the responses decreased, but the optimal direction of preference was usually retained. The contribution of binaural processing to auditory spatial tuning was evident, since unilateral cochlea ablation destroyed the spatial tuning at higher stimulus intensities. The results presented provide the first evidence that a topographically ordered representation of the contralateral auditory azimuth is present in the ICX of a mammal.

Microiontophoretic studies of the effects of D-1 and D-2 receptor agonists on type I caudate nucleus neurons: lack of synergistic interaction.

Several lines of evidence have suggested there may be a physiologically relevant form of synergistic interaction between D-1 and D-2 dopamine (DA) receptors located on postsynaptic neurons in the forebrain that receive a dopaminergic innervation. Because of the theoretical importance of such an interaction with respect to understanding the normal physiology of dopaminergic systems, we evaluated effects of D-1 and D-2 selective agonists, applied microiontophoretically, on the spontaneous electrical activity of a single, identifiable subpopulation of neurons within the caudate nucleus, the type I striatal neuron, in locally anesthetized, gallamine-paralyzed rats. It was observed that the D-2 receptor agonist quinpirole (QUIN) produced biphasic effects on cell firing rate. Low ejection currents significantly increased firing rate, while higher currents produced an inhibition. Similar effects were observed for the D-1 agonists SKF 38393; however, the overall excitations observed at low ejection currents were far less than those observed for QUIN. When these two agonists were applied concurrently, a simple additive effect (but not synergism) was always observed. The acute reduction of striatal levels of DA, by as much as 84% (with pretreatment with alpha-methyl-p-tyrosine, AMPT), did not alter the responsiveness of type I striatal neurons to the DA receptor agonists applied alone or in combination. These observed effects were not altered either by chloral hydrate anesthesia (in which glutamate-driven activity was studied) or by a more severe depletion of striatal DA levels (98% depletion produced by combined pretreatment with AMPT and reserpine).

Expiratory bulbospinal neurons of dogs. I. Control of discharge patterns by pulmonary stretch receptors

To better understand expiratory bulbospinal (EBS) neuronal processing of afferent patterns from slowly adapting pulmonary stretch receptors (PSRs), the responses of these caudal medullary neurons to various inflation patterns were analyzed in thiopental sodium-anesthetized paralyzed dogs. Normocapnic ventilation was obtained from lung inflations delivered during the neural inspiratory phase of control respiratory cycles by a solenoid ventilator triggered by the onset of phrenic nerve activity. Test inflation patterns, delivered during the neural expiratory (E) phase of specific cycles, were separated by 6-10 control cycles and consisted of slow augmenting and decrementing ramps and steps. Transpulmonary pressure (Pt) was used as an index of PSR activity, and the discharge patterns of single EBS neurons were quantified using cycle-triggered histograms. Based on the time course of the discharge pattern during no-inflation cycles, two types of neurons were identified. Type D, the most common, exhibited a decrementing-like pattern, while type A exhibited an augmenting-plateau pattern. Plots of discharge frequency vs. Pt for type D neurons consisted of a linear excitatory phase (1 less than Pt less than 4.6 mmHg) and a linear inhibitory phase (4.6 less than Pt less than 12 mmHg). Type A neurons exhibited only a linear inhibitory phase for 3.3 less than Pt less than 12 mmHg. Because the responses to step inflations (4 s duration) exhibited only a small amount of time dependency, and the activation Pt of PSRs, but not of the other pulmonary receptors with vagal fibers, is in the proper range, it appears that PSRs may mediate both excitatory and inhibitory components of the neuronal response. These data suggest that discharge patterns of the caudal EBS neurons in dogs are highly dependent on the time course of Pt in a predictable manner, and implicate the importance of instantaneous lung volume in the control of the E musculature and the optimization of the breathing pattern.

Sub-populations of pars compacta neurons in the substantia nigra: The significance of qualitatively and quantitatively distinct conductances

In the substantia nigra pars compacta neurons can be classified in two sub-populations. In this study the distinguishing criteria have been the presence of four distinct calcium-dependent potentials, two each generated selectively and exclusively in each cell type. One class of cells, found in the more caudal pars compacta, displays calcium-mediated, slow oscillatory potentials which occur spontaneously and generate long-duration afterhyperpolarizations. A second, much faster calcium spike can be evoked after the blockade of sodium and potassium channels. This spike has a high generation threshold and is followed by a fast afterhyperpolarization. The other group of neurons is distributed principally in the rostral substantia nigra, at the level of the mammilary bodies. In these cells, a low-threshold calcium spike is generated that (i) inactivates at depolarized potentials (ii) has no active negative phase, and (iii) causes burst firing action potentials. In all these three respects, this transient differs from the slow oscillatory potential in the more caudal group of neurons. In addition, a short-duration calcium-dependent potential can be evoked at a high threshold. Both the low- and high-threshold spikes of the rostral cells are attenuated in experiments where dendrites have been sectioned prior to the recording. The membrane properties of the caudal cell group, including the fast calcium spike, are unaffected by dendritic sectioning. It is suggested that in the guinea-pig the calcium conductances in the caudal neurons operate in or near the cell body and might play a large (though not necessarily exclusive) role in regulating autorhythmicity. In the more rostral cells, the characteristics of their particular calcium conductances which seem to be located more distally would prompt a mediating function in the secretion, and subsequent action, of neuroactive substances from dendrites.

Caudate nucleus pathology in Parkinson's disease: ultrastructural and biochemical findings in biopsy material.

Ultrastructural and biochemical properties of caudate nucleus (CN) biopsies in two patients with advanced Parkinson's disease (PD) were compared with three CN specimens removed during surgery for intracranial tumors. An additional two specimens from neurologically intact patients (59 and 86 years old) were removed during autopsy (performed 3 and 4 h post mortem, respectively) for electron microscopic studies. Dopamine levels in PD were reduced to less than 15% of control values. Both PD patients showed frequent dystrophic neurites and transsynaptic degeneration of neurons and neuritic processes. These changes were not found in CN from the four control individuals. Only a few dystrophic neurites were noticed in one 67-year-old control patient. The development of neuroaxonal dystrophy in CN is consistent with a dying-back process, probably accompanying abnormalities of axonal transport in PD. Transsynaptic degeneration of neurons in CN very likely represents a morphological marker of disease severity. The occurrence of this change may account for the poor clinical response of patients with advanced PD to intracerebral implantation of dopaminergic tissues.

Ionic mechanisms involved in muscarinic regulation of neuronal and paraneuronal activity.

The characteristics of neuronal and paraneuronal muscarinic inhibition and excitation were analyzed using rat caudate nucleus (CN) slices and isolated chromaffin cells obtained from the rat adrenal medulla. In CN neurons, either acetylcholine (ACh), carbachol, or muscarine inhibited orthodromically activated firing, while nicotine had no effect on neuronal activity. Muscarine decreased the amplitude of EPSPs without altering the resting membrane potential (RMP), input impedance and EPSP time courses. These results indicate that muscarinic receptors produce the presynaptic inhibition of synaptic transmission in the CN. In adrenal chromaffin cells, it was found that ACh, muscarine, and nicotine all increased extracellularly recorded firing. During voltage clamp recording at the RMP, ACh induced a transient inward current (fast response) followed by a long-lasting current (slow response). Muscarine induced the slow response, whereas nicotine induced the fast response. Muscarine reduced the inward K+ current produced by the application of a high K+ medium to cells. During patch clamp recording, muscarine decreased the opening rate of the single K+ channels. These results indicate that the muscarinic excitation of adrenal chromaffin cells was triggered by a reduction in the number of active K+ channels at the RMP.