Characteristics of background unit activity in the nucleus reticularis of the human thalamus

Background firing activity was examined in 240 neurons belonging to the thalamic nucleus reticularis (Rt) in the unanesthetized human brain by extracellular microelectrode recording techniques during stereotaxic surgery for dyskinesia. The cellular organization of Rt was shown to be nonuniform, and distinguished by the presence of three types of neuron: one with arrhythmic single discharge (A-type, 40%), another with rhythmic (2–5 Hz) generation of short high-frequency (of up to 500/sec) burster discharges (B-type, 49%) and a third with aperiodic protracted high-frequency (of up to 500/sec) bursting discharges separated by "silent" intervals of a constant duration of 80–150 msec (i.e., C-type, 11%). Differences between the background activity pattern of these cell types during loss of consciousness under anesthesia are described. Tonic regulation of neuronal type was not pronounced but a tendency was noticed in the cells towards a consistent rise in firing rate, rhythmic frequency and variability, etc. in both A and B units, especially in the latter. Findings pointing to the absence of a direct relationship between rhythmic activity in the Rt and parkinsonian tremor were confirmed. Background activity in B-type cells was found to increase and then stabilize with a rise in the degree of tremor. The nature of regular bursting activity patterns in B and C neurons is discussed in the light of our findings.Institute of Chemical Physics, Academy of Sciences of the USSR, Moscow. Institute of Neurosurgery, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 19, No. 4, pp. 456–466, July–August, 1987.     

Rhythmic activity of neurons in the rostral ventrolateral medulla of conscious cats: effect of removal of vestibular inputs

Although it is well established that bulbospinal neurons located in the rostral ventrolateral medulla (RVLM) play a pivotal role in regulating sympathetic nerve activity and blood pressure, virtually all neurophysiological studies of this region have been conducted in anesthetized or decerebrate animals. In the present study, we used time- and frequency-domain analyses to characterize the naturally occurring discharges of RVLM neurons in conscious cats. Specifically, we compared their activity to fluctuations in carotid artery blood flow to identify neurons with cardiac-related (CR) activity; we then considered whether neurons with CR activity also had a higher-frequency rhythmic firing pattern. In addition, we ascertained whether the surgical removal of vestibular inputs altered the rhythmic discharge properties of RVLM neurons. Less than 10% of RVLM neurons expressed CR activity, although the likelihood of observing a neuron with CR activity in the RVLM varied between recording sessions, even when tracking occurred in a very limited area and was higher after vestibular inputs were surgically removed. Either a 10-Hz or a 20- to 30-Hz rhythmic discharge pattern coexisted with the CR discharges in some of the RVLM neurons. Additionally, the firing rate of RVLM neurons, including those with CR activity, decreased after vestibular lesions. These findings raise the prospect that RVLM neurons may or may not express rhythmic firing patterns at a particular time due to a variety of influences, including descending projections from higher brain centers and sensory inputs, such as those from the vestibular system.     

GABAergic modulation of the oscillatory activity in the medial septal area during epilepsy

On brain slices from healthy guinea pigs and animals with a model of chronic temporal lobe epilepsy, a comparative study of GABAergic modulation of oscillatory activity of neurons in the medial septal area was carried out. Under the action of GABA, burst activity persisted only in pacemakers in both groups of preparations. In epilepsy, the effectiveness of GABA action on the rhythmic neurons sharply increased. In the control group, GABA significantly reduced bursts frequency in cells preserving their oscillatory activity, whereas in slices from the epileptic brain burst frequency increased under the action of GABA. Blockade of GABAergic receptors led to a disruption of tonic GABAergic intraseptal influences and to a significant decrease in the effectiveness of blockers in epilepsy. The study was the first to demonstrate a dysfunction of the septal GABAergic system in temporal lobe epilepsy, which is a possible cause of a sharp change in the oscillatory properties of septal neurons. These findings contribute to elucidation of the mechanisms of temporal lobe epilepsy.     

Effect of cortisol microiontophoresis on discharge time structure of dorsal hippocampal neurons in rabbits

The effect of microiontophoretic application of cortisol to single neurons of the dorsal hippocampus on the character of distribution of interspike intervals in their discharges was studied in chronic experiments on rabbits. Cortisol modified the time structure of regular and rhythmic discharges of hippocampal neurons. Regularization of discharges in the form of bursting activity appeared as the result of cortisol in cells with irregular spontaneous activity. Activity of more than half of the neurons, in which bursting discharges corresponded in frequency to the theta-rhythm, was intensified as a result of microapplication of cortisol. In neurons discharging complex spikes, in which under normal conditions a phenomenon of reduction of spike amplitude was observed within each burst, no definite rule as regards changes in the time structure of the discharges could be observed after administration of the hormone. It is suggested that cortisol plays a modulating role in mechanisms of generation of spike activity by hippocampal neurons.P. K. Anokhin Research Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 6, pp. 628–635, November–December, 1981.     

Cellular principles underlying normal and pathological activity in the subthalamic nucleus

The motor symptoms of Parkinson's disease are associated with abnormal, correlated, low frequency, rhythmic burst activity in the subthalamic nucleus and connected nuclei. Research into the mechanisms controlling the pattern of subthalamic activity has intensified because therapies that manipulate the pattern of subthalamic activity, such as deep brain stimulation and levodopa administration, improve motor function in Parkinson's disease. Recent findings suggest that dopamine denervation of the striatum and extrastriatal basal ganglia profoundly alters the transmission and integration of glutamatergic cortical and GABAergic pallidal inputs to subthalamic neurons, leading to pathological activity that resonates throughout the basal ganglia and wider motor system.     

Interaction between hindbrain and spinal networks during the development of locomotion in zebrafish

Little is known about the role of the hindbrain during development of spinal network activity. We set out to identify the activity patterns of reticulospinal (RS) neurons of the hindbrain in fictively swimming (paralyzed) zebrafish larvae. Simultaneous recordings of RS neurons and spinal motoneurons revealed that these were coactive during spontaneous fictive swim episodes. We characterized four types of RS activity patterns during fictive swimming: (i) a spontaneous pattern of discharges resembling evoked high-frequency spiking during startle responses to touch stimuli, (ii) a rhythmic pattern of excitatory postsynaptic potentials (EPSPs) whose frequency was similar to the motoneuron EPSP frequency during swim episodes, (iii) an arrhythmic pattern consisting of tonic firing throughout swim episodes, and (iv) RS cell activity uncorrelated with motoneuron activity. Despite lesions to the rostral spinal cord that prevented ascending spinal axons from entering the hindbrain (normally starting at approximately 20 h), RS neurons continued to display the aforementioned activity patterns at day 3. However, removal of the caudal portion of the hindbrain prior to the descent of RS axons left the spinal cord network unable to generate the rhythmic oscillations normally elicited by application of N-methyl-d-aspartate (NMDA), but in approximately 40% of cases chronic incubation in NMDA maintained rhythmic activity. We conclude that there is an autonomous embryonic hindbrain network that is necessary for proper development of the spinal central pattern generator, and that the hindbrain network can partially develop independently of ascending input.     

Comparative analysis of background activity of ventrolateral thalamic neurons in patients with parkinsonism and torsion muscle dystonia

In the course of neurosurgical interventions in 40 patients with parkinsonism and torsion muscle dystonia, the background activity (BA) was recorded from 124 neurons of the ventrolateral nucleus (VL) of the thalamus with the aid of microelectrodes during demarcation of boundaries between nuclear structures, and identification of zones within a nucleus. The following characteristic features of the BA in patients with parkinsonism were found: a relatively large proportion (71%) of cells with a burst pattern of activity; a great diversity of burst duration in the activity (short or prolonged bursts); a large proportion (67%) of cells with cyclic changes in the BA frequency; diverse patterns of cyclic modulation, where periods varied from fractions of a second (0.2–0.8 sec) to seconds (2–10 sec) or to tens of seconds (20–40 sec); cyclic successions of spike bursts with the rhythm typical of the peripheral tremor (3–7/sec) in a substantial proportion (40%) of the units.The background spike trains recorded in patients with torsion muscle dystonia consisted of separated spikes in the majority (69%) of units. Only short high-frequency discharges were found in the burst activity in this group; a cyclic BA pattern occurred much less frequently (in 23% of neurons); burst discharges at a 3–4/sec frequency were found only in 4% of the examined cells.The possible nature of motor disorders in patients with parkinsonism and torsion muscle dystonia and the mechanisms of the curing effects of cryodestruction of theVL of the thalamus in the treatment of the disease are discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 4, pp. 246–253, July–August, 1993.     

The excitability of neurons of the medial septal area in brain slices from hibernating and active Citellus undulatus susliks]

Spontaneous and evoked neuronal activity of the medical septum-diagonal band complex (MS-DB) has been investigated in slices from the brain of hibernating and active ground squirrels, as well as guinea pigs. In all experimental groups, the majority of the MS-DB neurones exhibited high regular of rhythmic burst spontaneous activity which persisted even after synaptic blockade in half of the neuronal population. Under the same conditions, the activity of the surrounding structures was completely suppressed. The density of the spontaneously active neurones in the slices, as well as the mean frequency of discharges in the MS-DB of hibernating ground squirrels, were significantly higher than in active ground squirrels and guinea pigs. Stimulation of the medial forebrain bundle evoked initial suppression of the activity in the majority of MS-DB units; in many of them, the suppression was followed by a burst discharge. Neurones with background rhythmic burst activity always reacted by resetting the spontaneous bursts. In total, 50-60% of the MS-DB neurones in active ground squirrels and guinea pigs reacted by post-inhibitory bursts, whereas in hibernating animals these responses were observed nearly in all neurones. Threshold values of the stimulating current were lower in hibernating animals; the intraburst density of spikes was increased.     

Spontaneous unit activity of locus coeruleus neurons after destruction of some nuclei of the medulla oblongata

Bilateral lesions of the nuclei prepositus hypoglossi produced a more than twofold decrease in the mean frequency discharges in the neurons of the nucleus coeruleus. The number of neurons with burst activity and the number of polymodal neurons substantially increased. Lesion of the nucleus tractus solitarius resulted in an increase in the number of neurons with regular activity and certain decrease in the mean discharge frequency of coeruleus neurons. The results confirm the suggestion about a substantial role of the nucleus prepositus hypoglossi in relaying afferent effects to the activity of locus coeruleus neurons.     

Functional changes in the septal GABAergic system of animals with a model of temporal lobe epilepsy

The septal GABAergic system plays a central role in the regulation of activity and excitability of the hippocampus (the main locus of temporal lobe epilepsy, TLE), but the character of changes the septum undergoes in this pathology remains unknown. To address this issue we studied the influences on GABAergic receptors in septal slices from the brain of epileptic guinea pigs compared to a control. In the epileptic brain, the overall increase in the mean frequency of neuronal discharges and the rise in the number of bursting neurons were revealed. The inhibitory action of exogenously applied GABA on neuronal activity is sharply enhanced, whereas the efficacy of action of GABA(A) and GABA(B) receptor blockers decreases, indicating the alteration of intraseptal inhibitory processes in epilepsy. In epilepsy, GABA sharply increases the oscillatory activity of the part of pacemakers, and the opposite effect was observed in the control. In epileptic animals, the GABA receptor blockers did not affect burst neurons, indicating the disturbance of the tonic GABAergic control of the oscillatory activity. Thus, we demonstrated for the first time that the activity of septal neurons and their reactions to GABAergic substances in animals with TLE model changed sharply compared to healthy ones.     

The spontaneous neuronal activity of the hippocampus during the modulation of the theta rhythm by cholinergic substances]

Background activity of the hippocampal neurons, extracellularly recorded in waking chronic rabbits, was analysed in control state and after systemic injection of physostigmine and scopolamine. Similar analysis was done in the hippocampus chronically deprived of ascending brain stem afferents. Cholinergic drugs controlled the number of hippocampal neurons with theta-modulation and the degree of its stability but not the frequency. Activation of cholinergic theta-rhythm resulted also in regularization of activity with suppression of delta-modulation and complex spike discharges; its blockade was accompanied by the opposite changes. Both drugs shifted the level of background activity in the majority of neurons, but the overall mean frequency did not vary between the states. Regression analysis demonstrated significant negative correlations with dominating decrease in the level of activity in high-frequency neurons ( > 25 sp/s) and its increase in low-frequency ones ( < 25 sp/s) after injection of both drugs. Stability of the overall mean frequency and uniformity of its shifts presumably indicate that the frequency, unlike the pattern of the background activity, is not directly controlled by the cholinergic septal input.     

Effect of anticholinergic drugs alone and in combination with nembutal on burst theta-neurons of the rabbit septum

Activity of neurones with rhythmic theta-bursts was recorded in the medial septum--diagonal band complex of the waking rabbits with intact and deafferented septum. Effects of anticholinergic (scopolamine, atropine) and cholinomimetic (physostigmine) drugs were investigated after i.v. injection. Cholinoblocking drugs in doses, suppressing the theta-rhythm in the hippocampal EEG, eliminated rhythmic activity in some cells with weak theta-modulation. Theta-bursts persisted in cells with stable continuous rhythmicity, though its regularity decreased in some of them. Strong reticular or sensory stimulation evoked an increase of burst frequency, involvement of additional septal cells into rhythmic activity and appearance of the theta-rhythm in the hippocampal EEG. Neither anticholinergic, nor cholinomimetic drugs influenced the frequency and basic characteristics of theta-bursts in any condition tested. The anticholinergic drugs have no selective effect upon low-frequency theta-bursts. The septohippocampal connections contain a significant non-cholinergic component. The theoretical concept of the septum as a sole source of the whole frequency band of the theta-rhythm is proposed.     

The role of GABA-ergic regulation in organizing spontaneous and evoked activity of the septal neurons

Effects of GABA, pentobarbital and picrotoxin upon spontaneous and evoked activity of neurones of the medial septal nucleus and the nucleus of the diagonal band (MS-DB) were investigated in the guinea pig septal slices. GABA and pentobarbital have similar effect upon all neurones, but the cells with a regular single spike and rhythmic burst activity of pacemaker type were less sensitive to their inhibitory influence. Picrotoxin affects neither frequency, nor pattern of activity. Electrical stimulation of the medial forebrain bundle evoked initial suppression of activity in majority of the neurones (74%); the remaining cells reacted mainly with an initial burst. GABA and pentobarbital increased the duration of the initial inhibition and revealed it in all cells with initial excitation in the control state. Picrotoxin did not influence this type of response, but revealed initial short-latency bursts in the cells with inhibitory effect in control state. The experiments show double nature of the effect of afferent stimulation controlling the activity of the MS-DB neurones. The mechanism of synchronization of the rhythmic activity in MS-DB, resulting in generation of the hippocampal theta-rhythm, is discussed.     

Network effects of glutamate on neuronal activity in the medial septum/diagonal band complex in vitro

Inter-neuronal interactions within the medial septum/diagonal band complex (MSDB) are of great interest as this region is believed to be the hippocampal theta rhythm pacemaker. However, the role of glutamatergic system in functioning of the septal cells is yet unclear. Here, we demonstrate for the first time the effects of glutamate in physiological concentration (1 microM) on the MSDB neuronal spontaneous and evoked activities in vitro. These effects (activation of 70% and inhibition of 30% of responsive neurons) differed in pacemaker and non-pacemaker cells. Pacemaker cells were always activated under glutamate, whereas non-pacemaker neurons could be either activated or inhibited. Indeed, in the burst pacemakers, glutamate increased the frequency of rhythmic activity. In a total MSDB neuron population, in 30% of neurons glutamate applications modified responses to the electrical stimulation by unifying the temporal parameters of neuron responses. Along with the increase in the theta-burst frequency, this indicates that the glutamatergic system is involved in the process ofintraseptal synchronization. Obtained data shed light on the role ofglutamatergic system in septal neuron interactions and broaden our understanding of theta oscillation mechanisms in the septo-hippocampal system.     

Development of spinal cord bioelectric activity in spinal chick embryos and its behavioral implications

Embryonic behavior of the chick is the product of spontaneous multiunit burst discharges within the ventral spinal cord. The present study describes the ontogeny of spinal cord burst discharges in embryos which were deprived of brain input by removing several neural tube segments of 2-day embryos at cervical or mid-thoracic levels. Characteristics of bioelectric activity present in both intact and chronically transected cords are: (a) the appearance of spike discharges; (b) the organization of unit discharges into synchronized multiunit bursts; (c) the establishment of intracord synchronization of burst discharges over wide expanses of cord tissue; (d) an increase in burst duration and complexity at 7 days due to the appearance of the burst afterdischarge; (e) an increase in the amount of burst activity from 6 to 13 days followed by a decline until hatching at 21 days; (f) a shift from periodic to irregular patterns of burst activity at 13 days; and (g) the existence of the cord burst discharge as a correlate of embryonic movement. Several differences were found between burst activity from chronic spinal and intact embryos: (a) cervical spinal embryos were significantly less active than controls from 15 through 19 days; and (b) long sequences of unusual repetitive burst afterdischarges appeared in chronic spinal embryos by 13 days. The results indicate that the transected embryonic spinal cord is remarkably autogenous in function, although patterns of activity unique to the transected cord appear and increase in prominence during later stages of incubation.     

Comparative characteristics of septal "burst" neurons after elimination of afferent effects of the reticular formation in the rabbit

Comparative analysis of characteristics of rhythmic theta-activity in the neurones of the medial septal nucleus and nucleus of diagonal band was performed in intact rabbits after. i. v. injection of pentobarbital, and in rabbits with chronic lesion of the ascending brain-stem afferent fibers. In both conditions theta-bursts disappeared in some cells with unstable periodic rhythmic modulation; substantial population of the septal units preserved regular burst activity. Main characteristics of theta-bursts were almost identical in both states, their mean frequency decreased to 3.5 Hz. The theta-rhythm in hippocampal EEG was usually absent; but low-frequency rhythmic activity could be evoked by electrical or sensory stimulation as well as by injection of bemegrid or physostigmine. The data show that the ascending brain-stem afferents control: the frequency of the bursts in a population of septal units regarded as bursting pace-maker cells; the total number of the septal cells secondarily (synaptically) involved into rhythmic activity. The effect of pentobarbital upon theta-rhythm results from elimination of these influences upon the septal cells.     

Formation of an excitation generator in the medullary gigantocellular nucleus following disturbance of inhibition by tetanus toxin

Unit activity was studied in the gigantocellular nucleus of decerebrate cats after injection of tetanus toxin into the nucleus. The toxin was used to disturb inhibition. An increase in amplitude and frequency of unit discharges, a marked increase in integral spontaneous and, in particular, evoked activity, an increase in the number of neurons with a "burst" type of activity, and prolonged maintenance of enhanced evoked activity were recorded in the poisoned nucleus. The increased activity in the part of the poisoned nucleus studied could be temporarily suppressed by injection of glycine into the nucleus or by strong direct electrical stimulation. It can be concluded from the results that a population of neurons with disturbed inhibitory connections forms an excitation generator. The nature of operation of such a generator is discussed and the possibility of simulating neurological syndromes by the creation of such generators in various parts of the CNS is argued.     

Tissue culture study of unit activity of the rat cerebral cortex

Spontaneous unit activity and morphological characteristics of visual cortical neurons from young rats aged 1 and 2 days were investigated during long-term culture (up to 34 days) of explants in vitro. Three types of spontaneous unit activity were found: single spikes, volleys, and grouped discharges. The types of spontaneous activity were found to depend on the duration of cultivation of the brain tissue. The discharge of single spikes, characteristic of neurons during the first 7–15 days in culture, subsequently was replaced by grouped discharges or volleys of spikes. The changes in unit activity were shown to coincide in time with morphological maturation of the synapses. In experiments in which strychnine (10 µg/ml) was added to the culture medium, a marked increase was observed in the mean frequency of spontaneous unit activity, accompanied by the appearance of discrete series of volley-type discharges. The genesis of spontaneous cortical unit activity is discussed on the basis of these findings.     

Interaction of serotonin and leu-enkephalin on the habituating central neurons of Helix pomatia L. in situ and in vitro

1. Habituating neurons (a, b and c) of Helix pomatia reacted to the serotonin (10(-5)-10(-4)M) with depolarization evoking oscillatory waves and burst firing at the range of -35 to -55 MP values. 2. Isolated habituating cells were hyperpolarized by serotonin and failed to generate membrane oscillation or bursting pattern. 3. Only the isolated habituating neurons reacted to the application of leu-enkephalin (10(-5)-10(-4)M) by depolarization. 4. Neither membrane oscillation nor burst firing were evoked by leu-enkephalin. 5. On the cells a, b and c leu-enkephalin modulated the serotonin effect through cyclic 3',5'-AMP system both in situ and in vitro. 6. The membrane oscillation and burst firing of the habituating cells are connected to the regulation of various rhythmic processes including pneumostoma movements.     

帕金森病丘脑底核神经元的电活动特点

本研究探讨了帕金森病(Parkinson′s disease, PD)患者丘脑底核(subthalamic nucleus, STN)神经元电活动的特点及其与PD症状的关系. 35例PD患者在接受手术治疗的同时, 应用微电极细胞记录和EMG记录技术, 记录手术靶点STN及其周围结构神经元的电活动以及手术对侧肢体的EMG. 应用分析软件甄别单细胞电活动, 分析其特点及其与肢体EMG的关系. 结果表明, STN及其周围结构具有特征性放电活动.在36个记录针道中, 共发现436个STN神经元, 平均放电频率44.0±20.5 Hz. 其中, 56%的神经元呈不规则簇状放电; 15%呈紧张性放电; 29%呈规则的簇状放电, 其放电节律与肢体震颤的EMG高度一致(r2=0.66, P<0.01), 称之为震颤细胞. 在PD震颤型患者的STN中发现大量震颤细胞, 且80%位于STN中上部, 而在PD僵直型患者的STN中均发现与运动相关的细胞电活动. 本研究提示, 通过微电极记录技术可准确地判断STN的位置和范围; 与震颤活动相关的细胞放电和与运动相关细胞的放电与PD症状有内在关系; STN参与PD运动障碍的病理生理过程.