Changes In Unit Activity Research Articles

Trans-Spinal Direct Current Stimulation Targets Ca2+ Channels to Induce Persistent Motor Unit Responses.

Trans-spinal direct current stimulation (tsDCS) is a neuromodulatory approach to augment spinal cord activity to improve function after neurological disease and injury. Little is known about the mechanisms underlying tsDCS actions on the motor system. The purpose of this study is to determine the role for a persistent inward current (PIC)-like response in motoneurons in mediating tsDCS actions. We recorded single motor units from the extensor and flexor carpi radialis muscles in healthy sedated rats and measured unit activity changes produced by cervical enlargement cathodal and anodal tsDCS (c-tsDCS; a-tsDCS). Both c-tsDCS and a-tsDCS immediately increased spontaneous motor unit firing during stimulation. After c-tsDCS was stopped, spontaneous firing persisted for a substantial period (165 ± 5s), yet after a-tsDCS activity shortly returned to baseline (27 ± 7s). Administration of the L-type calcium channel blocker Nimodipine reduced spontaneous motor unit firing during c-tsDCS and blocked the persistent response. By contrast, Nimodipine did not change unit firing during a-tsDCS but the short persistent response was blocked. Computer simulation using a two-compartment neuronal model replicated the main experimental observations: larger and more persistent responses during and after c-tsDCS than a-tsDCS. Using reduced Ca2+ conductance to model Nimodipine action, a reduced response during c-tsDCS and elimination of the persistent response was observed. Our experimental findings, supported by computer simulation, show that c-tsDCS can target Ca2+ conductances to augment motoneuron activity. As tsDCS is well-tolerated in humans, this knowledge informs therapeutic treatment strategies to achieve rehabilitation goals after injury; in particular, to increase muscle force.

Emergence of prefrontal neuron maturation properties by training recurrent neural networks in cognitive tasks

SummaryWorking memory and response inhibition are functions that mature relatively late in life, after adolescence, paralleling the maturation of the prefrontal cortex. The link between behavioral and neural maturation is not obvious, however, making it challenging to understand how neural activity underlies the maturation of cognitive function. To gain insights into the nature of observed changes in prefrontal activity between adolescence and adulthood, we investigated the progressive changes in unit activity of recurrent neural networks as they were trained to perform working memory and response inhibition tasks. These included increased delay period activity during working memory tasks and increased activation in antisaccade tasks. These findings reveal universal properties underlying the neuronal computations behind cognitive tasks and explicate the nature of changes that occur as the result of developmental maturation.

Emergence of Prefrontal Neuron Maturation Properties by Training Recurrent Neural Networks in Cognitive Tasks

Working memory and response inhibition are functions that mature relatively late in life, after adolescence, paralleling the maturation of the prefrontal cortex. The link between behavioral and neural maturation is not obvious, however, making it challenging to understand how neural activity underlies the maturation of cognitive function. To gain insights into the nature of observed changes in prefrontal activity between adolescence and adulthood, we investigated the progressive changes in unit activity of Recurrent Neural Networks (RNNs) as they were trained to perform working memory and response inhibition tasks. These included increased delay period activity during working memory tasks, and increased activation in antisaccade tasks. These findings reveal universal properties underlying the neuronal computations behind cognitive tasks and explicate the nature of changes that occur as the result of developmental maturation.

State-Dependent Cortical Unit Activity Reflects Dynamic Brain State Transitions in Anesthesia

Understanding the effects of anesthesia on cortical neuronal spiking and information transfer could help illuminate the neuronal basis of the conscious state. Recent investigations suggest that the brain state identified by local field potential spectrum is not stationary but changes spontaneously at a fixed level of anesthetic concentration. How cortical unit activity changes with dynamically transitioning brain states under anesthesia is unclear. Extracellular unit activity was measured with 64-channel silicon microelectrode arrays in cortical layers 5/6 of the primary visual cortex of chronically instrumented, freely moving male rats (n = 7) during stepwise reduction of the anesthetic desflurane (6%, 4%, 2%, and 0%). Unsupervised machine learning applied to multiunit spike patterns revealed five distinct brain states. A novel desynchronized brain state with increased spike rate variability, sample entropy, and EMG activity occurred in 6% desflurane with 40.0% frequency. The other four brain states reflected graded levels of anesthesia. As anesthesia deepened the spike rate of neurons decreased regardless of their spike rate profile at baseline conscious state. Actively firing neurons with wide-spiking pattern showed increased bursting activity along with increased spike timing variability, unit-to-population correlation, and unit-to-unit transfer entropy, despite the overall decrease in transfer entropy. The narrow-spiking neurons showed similar changes but to a lesser degree. These results suggest that (1) anesthetic effect on spike rate is distinct from sleep, (2) synchronously fragmented spiking pattern is a signature of anesthetic-induced unconsciousness, and (3) the paradoxical, desynchronized brain state in deep anesthesia contends the generally presumed monotonic, dose-dependent anesthetic effect on the brain.SIGNIFICANCE STATEMENT Recent studies suggest that spontaneous changes in brain state occur under anesthesia. However, the spiking behavior of cortical neurons associated with such state changes has not been investigated. We found that local brain states defined by multiunit activity had a nonunitary relationship with the current anesthetic level. A paradoxical brain state displaying asynchronous firing pattern and high EMG activity was found unexpectedly in deep anesthesia. In contrast, the synchronous fragmentation of neuronal spiking appeared to be a robust signature of the state of anesthesia. The findings challenge the assumption of monotonic, anesthetic dose-dependent behavior of cortical neuron populations. They enhance the interpretation of neuroscientific data obtained under anesthesia and the understanding of the neuronal basis of anesthetic-induced state of unconsciousness.

Spontaneous motor unit behavior in human thenar muscles after spinal cord injury.

Our first aim was to characterize spontaneous motor unit activity in thenar muscles influenced by chronic cervical spinal cord injury. Thenar surface electromyography (EMG), intramuscular EMG, and abduction and flexion forces were recorded. Subjects were instructed to relax for 2 min. Units still firing after 10 s were considered spontaneously active. Two distinct patterns of spontaneous unit activity were recorded. Units either fired tonically at a mean frequency of 6.1 HZ or were active sporadically (2.2 HZ). Stimuli (e.g., light touch of nearby skin) were then used to influence tonic spontaneous unit activity. Most stimuli produced a change in firing frequency, usually a temporary increase, but sometimes unit frequency decreased or new activity was initiated. Inputs to these motoneurons clearly make important contributions to changes in unit activity. However, the difficulty that subjects had in stopping unit activity, and the initiation of activity when subjects relaxed, suggest that the source of spontaneity may be the motoneuron itself.

Common Firing Patterns of Hippocampal Cells in a Differential Reinforcement of Low Rates of Response Schedule

Lesion studies show that the hippocampus is critically involved in timing behavior, but so far there has been little analysis of how it might encode time. We recorded the activity of 266 CA1 neurons, 51 CA3 neurons, and 219 entorhinal neurons from rats performing on a differential reinforcement of low rates (DRL) 15 sec schedule in which reinforcement was contingent on responses that occurred at least 15 sec after the preceding response. The unit data were analyzed using two different methods. First, each unit was subjected to an ANOVA that examined the effects of the following: (1) the outcome of the previous response (reward or nonreward); (2) the outcome of the response on which the firing of the cell was synchronized; and (3) time. This showed that, for CA1, CA3, and entorhinal cortex, changes in unit activity were related to all aspects of the task, with the firing of >90% of units recorded in each region being related to at least one of the three factors. Second, intercorrelations between the firing profiles of individual units revealed several functional categories of hippocampal neurons but no clear categories of entorhinal neurons. Of the hippocampal categories, the most common profile was an initial increase in unit activity at the beginning of the DRL interval, followed by a gradual decrease throughout the interval. We suggest that this profile reflects temporal decay in circuits that may code details of the previous trial and that could be used to "time" the DRL interval.

Comparison of touch- and laser heat-evoked cortical field potentials in conscious rats

Field potentials and multiunit activities from chronically implanted cortical electrodes were used to study tactile and nociceptive information processing from the tail of the rat. Fourteen stainless steel screws implanted in the skull were used as electrodes to record field potentials in different cortical areas. Electrical, mechanical, and laser pulses were applied to the tail to induce evoked cortical field potentials. Evoked responses were compared before and after sodium pentobarbital anesthesia (50 mg/kg, i.p.). In both electrical- and mechanical-evoked potential (EEP and MEP) studies, two major peaks were found in the conscious animal. The polarity of the late component was modified after pentobarbital anesthesia. In the laser-evoked potential (LEP) study, two distinct negative peaks were found. Both peaks were very sensitive to anesthesia. Following quantitative analysis, our data suggest that the first positive peak of EEP and MEP corresponded to the activation of the Aβ fiber, the second negative peak of MEP and the first peak of LEP corresponded to Aδ fiber activation, while the second peak of LEP corresponded to C fiber activation. The absolute magnitudes of all cortical components were positively related to the intensity of the stimulation. From spatial mapping analysis, a localized concentric source of field potential was observed in the primary somatosensory cortex (SI) only after activation of the Aβ fiber. Larger responsive cortical areas were found in response to Aδ and C fiber activation. In an intracortical recording experiment, both tactile and nociceptive stimulation evoked heightened unit activity changes at latencies corresponding to respective field potentials. We conclude that different cortical areas are involved in the processing of A and C fiber afferent inputs, and barbiturate anesthesia modifies their processing.

Subcortical Multiple Unit Activity Changes During Rat Male Sexual Behavior

Hernandez-Gonzalez, M., M. A. Guevara, G. Morali and M. Cervantes. Subcortical multiple unit activity changes during rat male sexual behavior. Physiol Behav 61(2) 285–291, 1997.—Multiple unit activity (MUA) was recorded from the ventral tegmental area (VTA) and mesencephalic locomotor region (MLR) during copulatory behavior of freely moving male rats. Simultaneous accelerometric recordings of the copulatory pelvic thrusting performed by the male rat were taken to precisely correlate in time the changes in MUA with well defined elements of copulation. The baseline MUA firing rates recorded in the quiet-alert condition in the VTA and in the MLR were significantly increased during pursuit of the female by the male; significantly higher MUA firing rates were found in the VTA at the 500 ms periods before and during the execution of pelvic thrusting in mount, intromission, and ejaculation responses as compared to the baseline, and returned to this value when these responses ended. The maximum MUA firing rate in the MLR was obtained during the execution of pelvic thrusting in each copulatory response, and it remained significantly elevated, as compared to the baseline, after thrusting and at the postintromission and postejaculatory genital grooming, then decreasing to basal values at the initial part of the postejaculatory interval. The fact that the highest changes in MUA were related to pelvic thrusting suggests a major participation of both structures in the execution of motor copulatory responses.

Eye movements modulate activity in hippocampal, parahippocampal, and inferotemporal neurons

1. Inferotemporal, hippocampal, and parahippocampal units were recorded while monkeys were alert (as judged by eye movements) but resting, in both light and dark. 2. Spontaneous saccadic eye movements produced significant changes in unit activity for 108 of 308 cells. This activity is shown to be extraretinal either because it occurred in complete darkness or because of its timing relative to the eye movement. 3. The total saccadic modulation in the ventral temporal lobe is estimated to be over ten million action potentials.

Broad directional tuning in spinal projections to the cerebellum.

1. Spinocerebellar neurons that project in the dorsal spinocerebellar tract (DSCT) receive mono- and polysynaptic inputs from specific sensory receptors in the hindlimb, and they project mossy fiber terminals to the cerebellar vermis. We examined the functional organization of these neurons and found that it relates to whole-limb parameters like limb posture and direction of limb movement. 2. We recorded the activity of 444 DSCT units during passive perturbations of the hind foot in anesthetized cats. The movements were either confined a single joint (the ankle; 234 cells) or involved the entire hindlimb (210 cells). The cells exhibited opposite responses for opposite directions of whole-limb movement, but a variety of response patterns for opposite directions of movement at one joint. We interpret the result to imply that the population encodes information about the whole limb rather than single joints. 3. Most of the 78 neurons recorded during passive limb placements (63%) responded to changes in limb length and also changes in limb orientation. In fact, the activity of most of the cells was broadly tuned with respect to the direction of passive limb movements generated by moving the hind foot in the sagittal plane. Changes in unit activity could be described by a cosine tuning function with respect to foot positions (72% of responses) and directions of foot movement (50%). 4. The similarity of this behavior to that of neurons in the motor cortex and cerebellar nuclei recorded during voluntary movements is consistent with a common neural code to represent the sensorimotor parameters of limb movement.

Serotonin (5-HT2) receptor mediated enhancement of cortical unit activity.

Simultaneous single-unit and intracortical activity were recorded from neocortical neurons in urethane-anaesthetized rats to investigate the role of serotonin (5-HT) in modifying cortical excitability. Units, at a depth of 775-1100 microns from the pial surface, discharged in a burst-pause pattern that was correlated with slow wave activity. Application of noxious somatic stimulation resulted in cortical desynchronization and altered the pattern of unit activity such that firing was continuous, i.e., the pauses were eliminated. Intravenous administration of the mixed 5-HT1C/5-HT2 antagonists (cinanserin, cyproheptadine, ketanserin, and ritanserin) prevented both desynchronization and the change in unit activity induced by noxious stimulation within 2.5-15 min of the injection. The basic pattern of burst-pause activity remained intact, but the number of spikes per burst was typically reduced, whereas interburst intervals were increased. Iontophoretic application of these antagonists onto cortical neurons resulted in actions similar to those observed following systemic administration. Intravenous and iontophoretic application of m-trifluomethylphenylpiperazine (5-HT1C agonist, 5-HT2 antagonist) resulted in actions indistinguishable from those observed with the above antagonists, from which we conclude 5-HT2 and not 5-HT1C receptors mediate the alteration in unit activity observed with noxious stimulation. The results are discussed with respect to an interaction between N-methyl-D-aspartate and 5-HT2 receptors leading to the enhanced unit activity observed with noxious stimulation.

Changes in unit activity of hippocampal area CA3 due to the neuroimmunomodulator neurotropin

As shown by animal experiments, low-dose trichlorodophenyl and dioctyl phthalate induce microsomal cytochrome P-450-dependent enzymes and ultrastructural changes in hepatocytes. This evidences hepatotoxicity of the compounds.

The Effects of Activation or Inhibition of the Subthalamic Nucleus on the Metabolic and Electrophysiological Activities Within the Pallidal Complex and Substantia Nigra in the Rat.

The changes in local cerebral glucose utilization (LCGU) and neuronal unit activities in the subthalamic nucleus and its major target structures (the pars reticulata of the substantia nigra, the globus pallidus and the entopeduncular nucleus) following microinjection of a GABAergic antagonist (bicuculline methiodide, 0.08 nmol) or agonist (muscimol, 0.2 nmol) into the subthalamic nucleus were determined. The metabolic effect was assessed by measuring LCGU by quantitative [14C]-2-deoxyglucose autoradiography in ketamine-anaesthetized rats. Bicuculline methiodide induced increased LCGU in the ipsilateral globus pallidus, the entopeduncular nucleus and the substantia nigra pars reticulata. In contrast, muscimol decreased LCGU in these structures. The neuronal activities in the subthalamic nucleus and related structures increased following injection of bicuculline and decreased after injection of muscimol. The changes in LCGU within the structures directly related to the subthalamic nucleus were correlated with the changes in the unit activity either in the subthalamic nucleus and/or its projection structures. However, the amplitude of the relative changes in neuronal unit activity were greater than the changes in LCGU. Nevertheless, the results emphasize the functional role of the subthalamic nucleus as an activating structure within the basal ganglia.

Changes in unit activities of VPL thalamic neurons after focal cerebral ischemia in rats

Changes in unit activities of VPL thalamic neurons after focal cerebral ischemia in rats

Single-unit responses of serotonergic neurons to vasoactive drug administration in behaving cats

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN), heart rate (HR), and arterial blood pressure were recorded in freely moving cats during spontaneous behavior and in response to systemic administration of vasoactive drugs. The activity of serotonergic neurons varied in association with behavioral arousal but was unrelated to spontaneous fluctuations in HR and blood pressure. Bolus administration of phenylephrine hydrochloride and sodium nitroprusside (15-20 micrograms/kg iv) produced a rapid transient increase (35 mmHg) and decrease (49 mmHg), respectively, in mean arterial pressure (MAP). Infusion of phenylephrine and sodium nitroprusside (100 micrograms/ml) produced sustained hypertension (avg MAP 166 mmHg) and hypotension (avg MAP 49 mmHg), respectively. The activity of serotonergic neurons was not significantly altered in response to phenylephrine or sodium nitroprusside administration. Furthermore, no significant changes in unit activity were observed after hydralazine administration (1 mg/kg iv) despite prolonged reflex activation of sympathetic outflow. Thus the activity of DRN serotonergic neurons was unrelated to transient alterations in blood pressure and baroreceptor activity. These results suggest that changes in the activity of serotonergic DRN neurons are not involved in physiological mechanisms underlying reflex alterations in sympathetic (and parasympathetic) outflow invoked by hypertension and hypotension.

Conditioning-related changes of unit activity in the dorsal lateral geniculate nucleus of urethane-anaesthetized rats

Changes in geniculate unit activity of urethane-anaesthetized and freely moving rats were investigated during conditioning. The conditioned stimulus (CS) was a flash which was paired with an electrical stimulation of the tail as unconditioned stimulus (US). The discharge rates evoked by the CS during forward conditioning were significantly higher in responding units than those evoked by reversal of CS and US (backward conditioning) or by pseudoconditioning. Tail stimulation alone did not cause significant changes in the firing rate of most of the neurons. In 25% of the investigated neurons the facilitation of activity evoked by forward conditioning persisted during an extinction period of more than 15 min. The effect of conditioning on neuronal activity appeared to be comparable in urethane-anaesthetized rats and in freely moving ones which responded to the US with a slight freezing behavior.

Functional ablation of the olfactory bulb by spreading depression: Unit activity changes and transient anosmia

Cortical spreading depression (SD) is widely used to induce functional decortication. Development of a reliable technique for eliciting SD in the olfactory bulb (OB) of rats makes it possible to achieve functional elimination of the first relay of the olfactory pathway. In order to assess the unit activity changes accompanying OBSD, adult male hooded rats (N=31) were anesthetized with pentobarbital and activity of OB units was recorded with carbon fiber microelectrodes. The predepression activity (12.7±0.8Hz) increased up to 35.1 ± 4.1 Hz during the burst which attained maximum 44±6 sec after K + acetate injection and corresponded to the steep depolarization phase of SD slow potential. The burst lasted 20.4±2.9 sec on the average and was followed by 187 ± 20 sec of complete silence. Gradual recovery to the predepression level lasted 229±27 sec. Activity of most units (63%) in the contralateral OB was not changed. Significant reactions of OB neurons to ipsilateral cortical SD found in 57% units were mostly inhibitory (49%). OBSD-induced anosmia was examined in a group of rats (n=8) with unilateral bulbectomy and a guiding tube implanted into the remaining OB for microinjection of K + acetate. One week after surgery, the animals were examined in the food-retrieval olfactory test. The microinjection of K + acetate severely disrupted the food finding behavior in 60% rats during 3-min test. Both electrophysiological and behavioral results indicate that OBSD is a convenient tool for inducing short-lasting anosmia.

Conditioning to time: Evidence for a role of hippocampus from unit recording

Unit activity of the dorsal hippocampus was recorded in partially restrained but awake and undrugged rats during a “conditioning to time”. In this type of conditioning, only one stimulus, the equivalent of the unconditioned stimulus of the usual procedures, is used. It is delivered at a constant interval which, in principle, is the conditioned stimulus. In our experiments, the unconditioned stimulus was a mechanical stimulation of a vibrissa; two successive unconditioned stimuli were separated by a 24-s interval. In 11/18 rats, anticipatory movements of a “trained” vibrissa developed at the end of the interstimulus interval. In a number of cases, in parallel to this conditioned behavior, there was a significant change in unit activity, either an increase or a decrease, during the last third of the interstimulus interval. Controls showed that these changes in unit activity did not merely reflect modifications of arousal state or of vibrissa and body movements. From autocorrelograms, it appeared that anticipatory increases in unit activity were associated with the development of a bursting mode of discharge. These data constitute one of the rare examples of a neurophysiological correlate of a “conditioning to time” at the unit Ievel and the first recorded from the dorsal hippocampus of rats.

“Learned” changes in the responses of the rat barrel field neurons

The effect of pairing two vibrissa stimulations on unit responses of the barrel field of the somatosensory cortex were studied in partially restrained but awake and undrugged rats. Before pairing, one of the stimulations (S2) evoked a stable, short-latency and excitatory response from the recorded unit. Depending on the neuron, the other stimulation (S1), preceding S2 by 500 ms, did or did not have an effect before pairing. In a number of cases, the S1-S2 association produced significant changes in the unit responses: (1) the appearance of an excitatory response to S1 when that stimulus was ineffective before pairing; (2) the modification of pre-existing responses to S1 and/or S2. In all instances these modifications consisted in the decrease or disappearance of the “afferent inhibition” and/or the appearance of long-latency excitatory components. These effects appeared after some 30–100 trials and persisted in some cases up to 20 min after interruption of pairing. Our observations provide the first physiological data on the plasticity of the vibrissa projections in the chronic adult rodent. Though the underlying plastic neural elements and mechanisms remain to be specified, these phenomena suggest that “learned” changes in unit activity may occur in sensory systems and not only in “non-specific” ones.

A comparison of the electrophysiological and pharmacological properties of serotonin-containing neurons in the nucleus raphe dorsalis, raphe medianus and raphe pallidus recorded from mouse brain slices In Vitro : Role of autoreceptors

The potential role of autoreceptors in regulating the activity of serotonin-containing nucleus raphe dorsalis (RD), raphe medianus (RM) and raphe pallidus (RPA) neurons was examined by recording the activity of these neurons under a variety of conditions both in vivo and in vitro. Raphe neurons recorded in vivo displayed the characteristic slow, rhythmic discharge pattern previously described for rat and cat raphe cells. The activity of these neurons was suppressed in a dose-dependent manner by tryptophan, LSD and chlorimipramine administered intravenously. There were no significant changes in the spontaneous discharge rate of raphe neurons over time when recorded in vitro, even though tissue serotonin and its metabolite, 5-hydroxyindoleacetic acid, decreased dramatically. RPA neurons fired significantly faster than either RD or RM neurons both in vivo and in vitro. Prior depletion of brain serotonin by p-chlorophenylalanine administration resulted in no significant change in raphe unit activity recorded in vitro. Elevation of brain serotonin by monoamine oxidase inhibition produced a total inhibition of raphe unit activity in vitro. Similarly, increasing the concentration of serotonin in the tissue slice by adding serotonin directly to the incubation medium resulted in a profound, though transitory, depression of unit activity. This depressant effect of serotonin was rapidly reversible upon drug wash-out. Serotonin receptor blockers, methiothepin, cypoheptadine, and methysergide, produced no significant change in unit activity. The serotonin reuptake blocker, fluoxetine, produced a total inhibition of raphe unit activity in all three nuclei in vitro. These data suggest that excess serotonin suppresses the activity of raphe neurons, apparently by an action on autoreceptors, but that a deficiency, or normal concentration, of serotonin does not influence the spontaneous activity of these cells. The data also show that RD and RM are much more sensitive to the depressant effects of serotonin than the caudal RPA neurons. More generally, these studies provide a data base for examining the electrophysiological and pharmacological characteristics of serotonergic neurons in the three major serotonin-containing nuclei in mouse brain. The mouse has proven to be a much easier species than the rat to use in these types of studies, based on the finding that mouse brain slices are more viable in vitro than are rat brain slices.