Spontaneous Unit Activity Research Articles

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.

Peptides in the parabrachial nucleus modulate visceral input to the thalamus

The role of neuropeptides in ascending visceral pathways was investigated by recording the changes in the response of thalamic neuronal activity evoked by vagal stimulation before and after peptide injection in the parabrachial nucleus (PB). Male Wistar rats (n = 25) were anesthetized with chloral hydrate and ventilated, and blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity in the parvocellular visceral relay nuclei in the ventral basal thalamus. Peristimulustime histograms of thalamic activity were made before and after 200-nl injections of peptides or artificial cerebrospinal fluid (CSF) controls in the PB. Injection of calcitonin gene-related peptide (CGRP) at 5 mM or substance P (SP) at 2 mM into the PB significantly attenuated the evoked response of thalamic neuronal activity by 87-100% and 85-100%, respectively. Injections of somatostatin (SOM; 1 mM) did not significantly alter the response evoked by vagal stimulation but significantly inhibited the spontaneous firing of thalamic units, resulting in a 10-fold increase in the response-to-background ratio. This suggests that SOM in the PB inhibits cells in a parallel pathway that terminates on thalamic visceral neurons but that are not part of the ascending visceral sensory pathway. Spontaneous thalamic neuronal activity and vagally evoked responses were significantly enhanced (278-508%) by injection of 1 mM neurotensin (NT) in the PB. Cholecystokinin (CCK) at low doses (0.0002-0.2 mM) attenuated while the highest dose, 2 mM, briefly excited the spontaneous activity of thalamic units before inhibiting their activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Responses of neurons in the rat anterior hypothalamic periventricular zone to osmotic stimulation and angiotensin II in vitro

Extracellular recordings were made in vitro from neurons in slices of the rat periventricular zone surrounding the anterior portion of the third ventricle. Spontaneous unit activity of these neurons was decreased in 39.5% of the neurons tested, increased in 32.9%, and biphasically changed (i.e., excitation-inhibition) in 10.5%, in response to bath application of hypertonic artificial cerebrospinal fluid (aCSF) containing elevated levels of NaCl (330 mOsm). Similar responses were observed following bath application of hypertonic aCSF prepared with additional mannitol. Angiotensin II in the perfusion medium dramatically increased spontaneous unit activity in 73.7% of neurons tested, while, unexpectedly, 5.3% were inhibited. These results suggest that some neurons in the periventricular zone are themselves osmosensitive, and may be involved in the regulation of water balance.

Striatal dysfunction in Rolling mouse Nagoya: an electrophysiological study

To elucidate the neuronal mechanism of the motor disturbances of the Rolling mouse Nagoya (rolling, genotype rol/rol), an experimental neurologic mutant mouse, we studied the physiological characteristics of neurons of the globus pallidus (GP) in rolling, comparing them with those of the behaviorally normal heterozygotes (+/rol) and normal controls (+/+). Forty-nine units in rolling, 41 in heterozygotes and 48 in controls were recorded under urethane anesthesia. The group mean of the interspike interval (ISI) of the spontaneous unit discharges was significantly shorter in rolling (42.2 ± 2.6 msec, mean ± SEM) than that of controls and of heterozygotes (55.4 ± 2.4 msec, P < 0.001 and 50.4 ± 2.6 msec, P < 0.05, respectively), indicating a significantly higher rate of spontaneous unit activity in the GP of rolling. In the controls and heterozygotes, about 60% of the GP neurons responded to striatal (ST) electrical stimulation with a predominantly inhibitory response, whereas a significantly smaller number of the GP neurons (22%, P < 0.001) exhibited inhibitory responses in rolling. The positive field potentials recorded in the GP evoked by ST stimulation were significantly smaller in amplitude in rolling (1.04 ± 0.10 mV, mean ± SEM) than that of the controls and heterozygotes (1.78 ± 0.15 mV, P < 0.001 and 1.97 ± 0.17 mV, P < 0.001, respectively). These results are in agreement with our previously reported findings of increased glucose metabolism and reduced concentration of GABA in the GP and substantia nigra pars reticulata (SNr) in rolling. We conclude that the major cause of motor disturbances of rolling is due to a primary dysfunction of the ST with a secondary dysfunction in its target structures such as the GP, entopeduncular nucleus, SNr and subthalamic nucleus.

Neuronal responses of the anterior commissural nucleus to osmotic stimulation and angiotensin II in hypothalamic slices in the rat

The firing rate and pattern of activity of neurons in the anterior commissural nucleus (ACN), which was rich in oxytocin-containing neurons, were studied electrophysiologically in hypothalamic slices. Extracellular recording showed that most ACN neurons exhibited irregular or regular continuous spontaneous unit activity. Other neurons showed short burst patterns of activity or were silent. The majority of ACN neurons were activated by bath application of angiotensin II, and a substantial number of them showed inhibitory or excitatory responses to hypertonic bathing medium. These results indicate that magnocellular neurosecretory neurons in the ACN may participate in the regulation of water balance.

Altered basal firing pattern and postactivation inhibition of locus coeruleus neurons in spontaneously hypertensive rats

We compared the spontaneous unit activity and inhibition of impulse activity following antidromic activation (postactivation inhibition, PAI) of locus coeruleus (LC) neurons in spontaneously hypertensive rats (SHR) with those of LC neurons in Wistar-Kyoto rats (WKY). Spontaneous spikes of the LC were analyzed by interspike time histograms. The basal unit activity and variation coefficient of the interspike interval were decreased in SHR. The duration of the PAI which was yielded by antidromic activation from the dorsal noradrenergic bundle was shortened in SHR. These findings suggest that SHR LC neurons possess an altered basal firing pattern and inhibitory mechanism.

Plasticity mechanisms in vestibular compensation in the cat are improved by an extract of ginkgo biloba (EGb 761)

The effects of administration of an extract of Ginkgo biloba (EGb 761) on vestibular compensation was studied in unilateral vestibular neurectomized cats. This experimental model of CNS plasticity was investigated by using behavioral tests (postural disorders compensation, locomotor balance recovery, electrophysiological (spontaneous and evoked neck muscle activity) and neurophysiological (spontaneous firing rate recovery of deafferented vestibular cells) recordings, and immunocytochemical methods (synaptic loss and synaptic reoccupation within the deafferented vestibular nuclei). In all experiments, EGb 761 was administered over 30 days at daily doses of 50 mg/kg IP. The results showed a faster recovery in the EGb-treated group of cats as compared to an untreated control group. EGb administration strongly accelerated postural and locomotor balance recovery. Concomitantly, spontaneous neck muscle activity, vestibulo-collicreflexes and spontaneous firing rate of vestibular units located on the lesioned side were restored earlier. Morphological correlates characterized by a more rapid synaptic reoccupation were found in the deafferented medial vestibular nucleus by means of immunoreactive labelling using an antibody against a synaptic vesicle-associated protein (synaptophysin), but they displayed a longer time-constant in comparison with the behavioral and neurophysiological data. These results clearly demonstrate that EGb 761 acts on recovery mechanisms considered as key processes in vestibular compensation. They suggest that this substance would possess neurotrophic and/or neuritogenic properties improving functional recovery after CNS injury.

Kindling‐Induced Neuronal Plasticity in the Dorsal Hippocampus CA1 in Acutely Prepared Rabbits: Unit Activity Analysis

To elucidate kindling-induced neuronal plasticity single cell discharge analysis, responses consisting of action potentials orthodromically elicited in the dorsal hippocampus CA1 by a single electric shock to the neighboring region were serially observed before, during and after kindling i.e. the repetition of stimulus trains applied to the same hippocampal region in acutely prepared rabbits. Eventually, the orthodromic unit response with identical amplitudes, which were regarded as a single cell origin, gradually increased in the firing rate at the interictal stages during and after the kindling. Further, an inhibitory period following the unit responses, during which no spontaneous unit activity appeared, was remarkably prolonged during and after the kindling. Both the increase of the unit responses and the prolongation of the inhibitory period irreversibly lasted for hours once they occurred. Such unit activity analysis confirms kindling-induced excitatory and inhibitory synaptic plasticity.

Integration of neocortical embryonal grafts with the neocortex of host rats examined by leao's spreading cortical depression

Cortical spreading depression (SD) was used to assess the density and organization of neural elements in neocortical transplants and their connectivity with the host brain. Embryonal neocortex (E14) was transplanted into cavities in the frontoparietal cortex of 3-month-old rats. SD elicited in the cortex of anesthetized host rats ( n = 12) 3 to 8 months after transplantation did not penetrate into the grafts. SD could be elicited in large transplants but did not propagate to the surrounding host neocortex. Spontaneous unit activity in the transplants was affected by SD elicited in the neocortex of the host rats anesthetized with urethane. Most units ( n = 49) displayed excitatory-inhibitory (52%) or inhibitory (29%) reactions, whereas purely excitatory reactions were less frequent (8%). The results suggest that the packing density of neurons in the transplant can support SD but that the conditions at the graft-host boundary (glial scar, scarcity of neurons) stop SD propagation. High reactivity of the graft neurons to SD in the host neocortex indicates that afferentation from the host brain represents an important, predominantly excitatory contribution to the spontaneous activity of the transplant.

The role of the claustrum in the bilateral control of frontal oculomotor neurons in the cat

The effect of claustrum (CL) stimulation on the spontaneous unitary activity of ipsi and contralateral frontal oculomotor neurons, was studied in chloralose-anaesthetized cats. A total of 205 units was bilaterally recorded in the medial oculomotor area, homologous of the primate "frontal eye fields"; 127 neurons were identified as projecting to the superior colliculus; for 33 of these last units stimulation of the ipsilateral CL provoked an excitatory effect lasting 10-25 ms and appearing with a latency of 5-15 ms; on 8 units the excitatory effect was followed by an inhibition lasting 100-250 ms. Ninety-eight of the 127 neurons were also tested through activation of the contralateral CL: 13 cells showed an excitatory effect lasting 10-35 ms and appearing with a latency of 20-50 ms. In three of the thirteen units the excitatory effect was followed by an inhibition lasting 100-150 ms. Complete section of the corpus callosum abolished the contralateral CL effect, suggesting the existence of a direct claustro-contralateral oculomotor cortex pathway running through the corpus callosum. The results could support the hypothesis that the CL may play a role in the bilateral control of the visuomotor performance.

Properties of spontaneous unit activity of output cells in the olfactory bulb

Properties of spontaneous unit activity of output cells in the olfactory bulb

Effect of claustrum stimulation on neurons of the contralateral medial oculomotor area, in the cat

In chloralose-anaesthetized cats, the extracellular spontaneous unitary activity was recorded from 157 neurons, located in the medial oculomotor area. 98 units were identified as projecting onto the superior colliculus. Electrical stimulation of the contralateral claustrum provoked, on 13 of these cells, an excitatory effect, lasting 10–35 ms and appearing with a latency of 20–50 ms. Full length section of the corpus callosum totally abolished the contralateral claustrum effect. The results suggest that in the cat, the claustrum may have a role in the bilateral control of the visuo-motor performance.

Respiratory activity in retrotrapezoid nucleus in cat

An anatomic projection from the retrotrapezoid nucleus to the ventral respiratory group in cat was previously reported by our laboratory (J. C. Smith, D. E. Morrison, H. H. Ellenberger, M. R. Otto, and J. L. Feldman. J. Comp. Neurol. 281: 69-96, 1989). We now report on the properties of neurons in the retrotrapezoid nucleus, investigated with extracellular recording techniques in 10 chloralose-urethane anesthetized, paralyzed, mechanically ventilated cats. A ventral exposure of the medulla facilitated recording from neurons in the retrotrapezoid nucleus, located ventral to the facial nucleus near the medullary surface. Respiratory-modulated, as well as irregularly discharging, spontaneous unit activity was recorded within the retrotrapezoid nucleus. Twelve respiratory-modulated units in the retrotrapezoid nucleus exhibited inspiratory (8 units), expiratory (3 units), or multimodal (1 unit) discharge patterns. Chemical activation of an inspiratory unit in the retrotrapezoid nucleus by pressure ejection of DL-homocysteic acid (less than 0.5 nl of 10 mM solution) demonstrated that the respiratory-modulated activity originated from the cell soma and not fibers of passage coursing through the retrotrapezoid nucleus region. Electrical microstimulation (20-40 microA, approximately 70-microseconds duration, biphasic pulse) within the ipsilateral ventral respiratory group elicited antidromic activation of 7 units in the retrotrapezoid nucleus, three of which were not spontaneously active. Electrical stimulation (5-80 microA, 70-microseconds pulse width, 100 Hz, 400- to 500-ms trains) at sites within retrotrapezoid nucleus affected the respiratory motor output when delivered during late expiration, eliciting premature onset of inspiration. These results suggest that retrotrapezoid nucleus projections to the ventral respiratory group (and dorsal respiratory group) may influence respiratory timing and pattern, perhaps by conveying signals originating in the rostral ventrolateral medulla that result from ventral surface perturbations.

Modifications of the responses of barrel field neurons to vibrissal stimulation during theta in the awake and undrugged rat

In partially restrained but awake and undrugged rats, excitatory unit responses of the somatic cortex barrel field to vibrissal stimulation, were recorded in two conditions: during spontaneous episodes of theta and in the absence of this rhythm. Two main variables were considered: a signal-to-noise ratio and an index of the “afferent inhibition”. Both measures were extracted from peristimulus time histograms. “Theta effects” were characterized by an increase in signal-to-noise ratio and afferent inhibition. They were most important in neurons located in infragranular layers of the cortex; they went in the same direction but only approached significance in supragranular neurons; neurons of the granular layer were not affected. Spontaneous unit activity and latencies were not modified in any group. These data were obtained during a preliminary step of a sensory-sensory conditioning procedure which in some cases modified the receptive field of the neurons. Theta effects were less marked in future “conditioned” than in future non-conditioned neurons but this was probably due to the fact that conditioned neurons had significantly higher signal-to-noise ratio and afferent inhibition. The origin of these “theta effects”, hippocampal versus non-hippocampal, and their functional significance, relation to selective attention, are discussed.

Effects of acetylcholine on single cortical somatosensory neurons in the unanesthetized rat

Experiments have been performed on unanesthetized rats using a chronic restraint system. The animal's head was held in a stereotaxic apparatus by means of two metallic tubes fixed on the skull with dental cement. Electrodes consisted of a recording micropipette (filled with 1 M NaCl and 2% Pontamine Blue) attached to a multibarreled micropipette for iontophoresis. Electrode penetrations were reconstructed on camera lucida drawings of frontal brain sections. The overall percentage of spontaneously active somatosensory neurons was 77% with a mean spontaneous activity of 5.9 impulse/s ( n = 405). Yet differences were observed in the proportions of active cells as well as in the mean spontaneous activity between cortical layers (both parameters being significantly higher in layers V and VI). Comparison with results obtained under urethane anesthesia [Dykes R.W. and Lamour Y. (1988) J. Neurophysiol. 60, 703–724] shows that the percentage of the spontaneously active neurons and the mean spontaneous activity were both significantly higher in unanesthetized rats (77 vs 36%; 5.9 vs 2.6 impulse/s). Nevertheless, the laminar distribution of the most active cells was similar under both conditions. In the present study, 52.3% of the neurons ( n = 380) were excited by acetylcholine and 46% ( n = 198) by carbachol. Significantly larger percentages of neurons excited by acetylcholine were found in layers Vb and VIb. These effects of cholinergic agonists—observed for the first time in unanesthetized rats—differed significantly from those previously obtained under anesthesia (33 and 34% of neurons excited by acetylcholine and carbachol, respectively) [Lamour Y. et al. (1982) Neuroscience 7, 1483–1494]. In the absence of anesthesia, cholinoceptive neurons were significantly more numerous in layers II–III. However, under both conditions, the highest percentages of excitatory responses were observed in layers Vb and VIb. A strong relation between the level of spontaneous unitary activity and the probability of being excited by acetylcholine was observed.

Reversible inactivation of the medial septum: selective effects on the spontaneous unit activity of different hippocampal cell types

The contribution of septal afferents to spontaneous hippocampal single unit activity was examined by reversibly inactivating the medial septal nucleus using microinjections of the local anethetic lidocaine. Septal inactivation reduced spontaneous firing of cells in stratum granulosum and in the hilar/CA3 region for periods of up to about 15 min. The firing rates of CA1 complex-spike (pyramidal) cells, however, were not changed, although CA1 theta cells (inhibitory interneurons) exhibited a significant reduction in spontaneous rate. One interpretation of this pattern of results is that the output of CA1 pyramidal cells is maintained roughly constant in spite of reduced input from CA3 because of a proportional reduction in feedforward inhibition. This interpretation is consistent with Marr's 22 formulation of the manner in which the hippocampus implements distributed associative memory. Alternatively, afferents to CA1 originating from regions other than CA3 may play a larger role in regulating CA1 output than previously assumed.

Effect of claustrum activation on the spontaneous unitary activity of frontal eye field neurons in the cat

The influence of claustrum stimulation on spontaneous unitary activity of the ipsilateral frontal oculomotor area was analyzed in anesthetized cats. Sixty-five neurons were isolated, 37 of which (57%) were identified as projecting to the superior colliculus; on 12 of these last units (32%), electrical activation of the dorsal claustrum provoked an excitatory effect, which appeared after a latency of 5–15 ms and lasted 10–25 ms. These data could suggest the involvement of the claustrum in the visuomotor coordination function.

A comparison of supramammillary and medial septal influences on hippocampal field potentials and single-unit activity

1. A comparison was made between the influences of supramammillary (SUM) and medial septal (MS) nuclei on hippocampal physiology in Nembutal-anesthetized rats. Specifically, the effects of prestimulation of the SUM or MS on the perforant path-dentate field potential, on spontaneous activity of single units, and on perforant path-induced unit activation were assessed. Another series of experiments addressed the issue of whether the SUM and MS effects on the perforant path-dentate field response are independent. 2. Prestimulation of the SUM or MS significantly facilitated the perforant path-dentate population spike with no clear effect on the field excitatory postsynaptic potential (EPSP) recorded in the subgranular zone of the dentate hilus. Prestimulation of either nucleus also reduced the threshold for spike onset. The major differences between the two spike facilitation effects were the magnitude of the change and possibly the optimal interstimulus intervals required to obtain the effects. 3. Acute transection of the ipsilateral column of fornix or dorsal fornix eliminated the SUM population spike facilitation effect. MS lesion or dorsal fornix/fimbria transection eliminated the MS spike facilitation effect. The MS lesion did not alter the effects of SUM prestimulation. Cingulum or medial forebrain bundle transection affected neither SUM- nor MS-mediated spike facilitation. Thus the SUM and MS influences on the dentate field response appear to be independent of one another. The relevant SUM afferents travel through the ipsilateral column of fornix and dorsal fornix, whereas MS afferents project through the dorsal fornix/fimbria. 4. Single units recorded in stratum granulosum (SG) were assessed with respect to several parameters. These included the mean firing rate, whether or not excitation occurred prior to the field population spike and at lower threshold, and whether or not a driven unit responded to a second perforant path stimulus delivered at short latency following the first (during the period of population spike depression). The latter parameter in particular appeared to separate SG cells into two classes. The cells that were not activated during the second field potential were classified as granule cells, whereas those that were activated were classified as basket cells. Based on this distinction, significant differences were also found between the two cell classes on the other parameters. In particular, cells classified as granule cells often had very low firing rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of anesthesia on spontaneous activity and receptive field size of single units in rat Sm1 neocortex

Spontaneous and cutaneously driven unit activity was recorded in the hindfoot region of rat Sm1 neocortex under controlled intravenous infusion, at three selected rates, of the steroid anesthetic agent Althesin. Increasing depth of anesthesia decreased average spontaneous firing rates of 67 single units from 2.5 to 11 Hz during light anesthesia to 0 to 2.5 Hz in deep anesthesia. Thresholds to cutaneous stimulation for 58 units were innocuous (from 15 to 190 μm) using a 5-ms ramp displacement of the skin in the center receptive field. Responses from 13 sites on the hindfoot were classified according to response probability for each of the 58 units in reply to stimuli at 1.5 times center receptive field threshold. Small receptive fields were seen only under conditions of deep anesthesia, considerable expansion of both center and excitatory surrounds occurring with lighter anesthesia. Mean values for total receptive field size (center plus surround excitatory receptive field) were 10.8, 7.8, and 3.4 sites, respectively, for light, moderate, and deep anesthesia. The size of the receptive field was also influenced by stimulus repetition rate; moderate increases of this and anesthetic depth could eliminate substantial receptive fields. Surround inhibition of evoked activity was more effective in deeper anesthesia with little effect in light anesthesia. We suggest that receptive field expansion in light anesthesia arises from a relative increase in excitability of afferent pathways and an accompanying increase in the preponderance of surround excitation vis à vis surround inhibition.

The effect of acute joint inflammation on flexion reflex excitability in the decerebrate, low-spinal cat.

Experiments were performed to investigate whether acute knee joint inflammation, induced by intra-articular injection of carrageenan and kaolin, significantly influences the magnitude of the flexion withdrawal reflex of knee flexors in the decerebrate, low-spinal cat. It was observed that after injection of these inflammatory agents, reflex intensity increased with a time course that matched the development of the inflammatory process, as assessed by monitoring the intra-articular temperature. Control experiments involving intra-articular injection of saline showed neither a rise in intra-articular temperature, nor any change in reflex intensity. The normal pattern of modulation of reflex intensity with changing joint angle was abolished in the inflamed joint with the reflex being equally intense at all positions tested. Abolition of neural activity in the inflamed joint by intra-articular injection of lignocaine resulted in a marked decrease in the reflex back to control values, suggesting that there is no maintained increase in central excitability in the absence of joint afferent input. It was also observed that the spontaneous activity of knee flexor motor units was modulated during continuous passive rotation of the knee, with activity being greater in extension than in flexion. This pattern reversed when the knee was acutely inflamed, but could be returned to the control pattern by joint anaesthesia, although now the response was attenuated when compared to the control.