Changes In Discharge Frequency Research Articles

Neuronal representation of working memory in the medial prefrontal cortex of rats.

Working memory is a process for short-term active maintenance of information. Behavioral neurophysiological studies in monkeys have demonstrated that the dorsolateral prefrontal cortex (dlPFC) is a key cortical region for working memory. The medial prefrontal cortex (mPFC) in rats is a cortical area similar to the dlPFC in monkeys in terms of anatomical connections, and is also required for behavioral performance on working-memory tasks. However, it is still controversial regarding whether and how mPFC neurons encode working memory. In the present study, we trained rats on a two-choice spatial delayed alternation task in Y maze, a typical working memory task for rodents, and investigated neuronal activities in the mPFC when rats performed the task. Our results show that, (1) inactivation of the mPFC severely impaired the performance of rats on the task, consistent with previous studies showing the importance of the mPFC for working-memory tasks; (2) 93.7% mPFC cells (449 in 479) exhibited changes in spiking frequency that were temporally locked with the task events, some of which, including delay-related cells, were tuned by spatial information; (3) differential delay activities in individual mPFC cells appeared transiently and sequentially along the delay, especially during the early phase of the delay; (4) some mPFC cells showed no change in discharge frequency but exhibited differential synchronization in firing during the delay. The present results suggest that mPFC neurons in rats are involved in encoding working memory, via increasing firing frequency or synchronization.

Sleep/Wake Firing Patterns of Human Genioglossus Motor Units

Although studies of the principal tongue protrudor muscle genioglossus (GG) suggest that whole muscle GG electromyographic (EMG) activities are preserved in nonrapid eye movement (NREM) sleep, it is unclear what influence sleep exerts on individual GG motor unit (MU) activities. We characterized the firing patterns of human GG MUs in wakefulness and NREM sleep with the aim of determining 1) whether the range of MU discharge patterns evident in wakefulness is preserved in sleep and 2) what effect the removal of the "wakefulness" input has on the magnitude of the respiratory modulation of MU activities. Microelectrodes inserted into the extrinsic tongue protrudor muscle, the genioglossus, were used to follow the discharge of single MUs. We categorized MU activities on the basis of the temporal relationship between the spike train and the respiration cycle and quantified the magnitude of the respiratory modulation of each MU using the eta (eta(2)) index, in wakefulness and sleep. The majority of MUs exhibited subtle increases or decreases in respiratory modulation but were otherwise unaffected by NREM sleep. In contrast, 30% of MUs exhibited marked sleep-associated changes in discharge frequency and respiratory modulation. We suggest that GG MUs should not be considered exclusively tonic or phasic; rather, the discharge pattern appears to be a flexible feature of GG activities in healthy young adults. Whether such flexibility is important in the response to changes in the chemical and/or mechanical environment and whether it is preserved as a function of aging or in individuals with obstructive sleep apnea are critical questions for future research.

Impact of Commitment on Performance Evaluation in the Rostral Cingulate Motor Area

Performance evaluation is a prerequisite for behavioral adaptation. Although the anterior cingulate cortex (ACC) is thought to play a central role in error detection, little is known about the electrophysiological activity of this structure during the performance-monitoring process. We directly addressed this issue by training monkeys to perform a Stroop-like task and then recorded neuronal activity in the rostral cingulate motor area (CMAr), a relatively unexplored region of the ACC known to be involved in motor processing. We found that most CMAr neurons responded during the evaluation period to both positive and negative feedback, but neuronal changes were more important after an error than after a successful trial. Interestingly, this performance-monitoring activity was not directly modulated by the degree of difficulty of the cognitive situation because changes in discharge frequency were similar whatever the level of attentional control imposed on the monkey. Firing activity during the evaluation period increased more, however, in erroneously completed than in incompleted trials and when the reward was delivered in an active rather than passive context, indicating that performance evaluation was conditioned by the degree of commitment of the animal to the task. It would thus seem that CMAr neurons could constitute a system for the evaluation of behavioral performance contingent on the subject's commitment to the task.

Effects of a cross-modal manipulation of attention on somatosensory cortical neuronal responses to tactile stimuli in the monkey.

The role of attention in modulating tactile sensitivity in primary (SI) and secondary somatosensory cortex (SII) was addressed using a cross-modal manipulation of attention, somatosensory versus visual. Two adult monkeys (Macaca mulatta) were trained to perform two tasks: tactile discrimination of a change in the texture of a surface presented to digits 3 and 4 and visual discrimination of a change in the intensity of a light. In each trial, standard texture (2 mm spatial period, SP) and visual stimuli were presented. These were followed by an increase in SP and/or luminance. Each trial was preceded by an instruction cue (colored light) that directed the animal to attend and respond to the change in one modality while ignoring any change in the other modality. The two tasks were interleaved during the recording, on a trial-by-trial basis. Extracellular recordings were made from 178 neurons (SI, 102; SII, 76), all with a cutaneous receptive field on the stimulated digit tips. Discharge was quantified in both tasks during the instruction, the standard-stimuli, and the texture-change periods. The results showed that selective attention to tactile stimuli had qualitatively and quantitatively greater and earlier effects in SII than SI. Twenty-four of 102 SI cells showed a significant change in discharge with the direction of attention. For almost all cells (20/24), discharge was enhanced when attention was directed toward the tactile stimuli; the effects were most frequent in the analysis interval that encompassed the change in SP (16/24). A significantly higher proportion of SII cells were attention-sensitive (47/76). The effects were concentrated in the texture-change period (39/47) but also included earlier periods in the trial (instruction period, n = 15; standard-stimuli period, n = 32). Attention-related modulation that spanned all three intervals (n = 11) likely reflected baseline changes in discharge. For the texture-sensitive cells (43 in SI, 37 in SII), the mean change in discharge frequency (post texture change - pre-texture change) in each task was significantly increased in SII but not SI with selective attention. The results are consistent with a two-stage modulation of parietal cortical discharge, an initial stage (SI) in which there is some enhancement of sensory responses to the salient feature, the texture change, and a second stage (SII) in which baseline changes occur, along with further feature selection. These controls may be independently exerted on SI and SII, or they may reflect top-down controls from SII to SI.

Vestibulospinal and reticulospinal neuronal activity during locomotion in the intact cat. II. Walking on an inclined plane.

The experiments described in this report were designed to determine the contribution of vestibulospinal neurons (VSNs) in Deiters' nucleus and of reticulospinal neurons (RSNs) in the medullary reticular formation to the modifications of the walking pattern that are associated with locomotion on an inclined plane. Neuronal discharge patterns were recorded from 44 VSNs and 63 RSNs in cats trained to walk on a treadmill whose orientation was varied from +20 degrees (uphill) to -10 degrees (downhill), referred to as pitch tilt, and from 20 degrees roll tilt left to 20 degrees roll tilt right. During uphill locomotion, a majority of VSNs (25/44) and rhythmically active RSNs (24/39) showed an increase in peak discharge frequency, above that observed during locomotion on a level surface. VSNs, unlike some of the RSNs, exhibited no major deviations from the overall pattern of the activity recorded during level walking. The relative increase in discharge frequency of the RSNs (on average, 31.8%) was slightly more than twice that observed in the VSNs (on average, 14.4%), although the average absolute change in discharge frequency was similar (18.2 Hz in VSNs and 21.6 Hz in RSNs). Changes in discharge frequency during roll tilt were generally more modest and were more variable, than those observed during uphill locomotion as were the relative changes in the different limb muscle electromyograms that we recorded. In general, discharge frequency in VSNs was more frequently increased when the treadmill was rolled to the right (ear down contralateral to the recording site) than when it was rolled to the left. Most VSNs that showed significant linear relationships with treadmill orientation in the roll plane increased their activity during right roll and decreased activity during left roll. Discharge activity in phasically modulated RSNs was also modified by roll tilt of the treadmill. Modulation of activity in RSNs that discharged twice in each step cycle was frequently reciprocal in that one burst of activity would increase during left roll and the other during right roll. The overall results indicate that each system contributes to the changes in postural tone that are required to adapt the gait for modification on an inclined surface. The characteristics of the discharge activity of the VSNs suggest a role primarily in the overall control of the level of electromyographic activity, while the characteristics of the RSNs suggest an additional role in determining the relative level of different muscles, particularly when the pattern is asymmetric.

Contractile properties of human nasal dilator motor units.

The technique of intramuscular microstimulation was used to activate facial nerve fibers while acquiring simultaneous twitch force measurements to measure the contractile properties and force-frequency responses of human nasal dilator (ND) motor units. Twitch force amplitude (TF), contraction time (CT), half-relaxation time (HRT), and the maximal rate of rise of force normalized to the peak force (maximum contraction rate, MCR) were recorded from 98 ND motor units in 37 subjects. The average CT, HRT, MCR, and TF were 47.9 +/- 1.8 ms, 42.6 +/- 2.1 ms, 28.6 +/- 1.8 s-1, and 1.06 +/- 0.1 mN, respectively. Neither CT nor HRT were significantly correlated with TF. The average CT and HRT were similar to values recorded for small muscles of the hand but were faster than the values recorded from human toe extensor motor units. However the lack of an association between twitch force and CT or HRT was similar to the findings obtained for both human hand and foot muscles. Force-frequency curves were recorded from eight ND motor units. The force produced by the eight motor units was recorded in response to stimuli delivered at 1, 5, 10, 15, 20, 25, 30, 35, and 40 Hz to assess force-frequency relationships. The mean twitch force of the eight motor units was 0.91 +/- 0.3 mN and the average tetanic force was 8.1 +/- 1.8 mN. Therefore the average twitch force was equal to 12.7% of the tetanic force. Fifty percent of the unit tetanic force was achieved at an average frequency of 16. 4 +/- 1.7 Hz, which is greater than the value recorded for human toe extensor motor units (9.6 Hz). Thus the force produced by the ND motor units was more sensitive to changes in discharge frequency over the range of approximately 10-30 Hz and less sensitive to changes in the range of 0-10 Hz because of their fast contractile properties. The mean slope of the regression lines that were fit to the steep portion of each force-frequency curve was 5.15 +/- 0.5% change in force/Hz. This value was greater than the slope measured for human toe extensor muscles (4.2% change in force/Hz). These observations suggest that force gradation by ND motor units is more sensitive to changes in stimulation frequency than human toe extensor motor units. We conclude that most ND motor units have fast contractile properties and that rate coding may play a significant role in the gradation of force produced by the ND muscle. Furthermore, the findings of this investigation have demonstrated that contractile speed and TF in a human facial muscle are not correlated. This supports previous findings obtained from human hand and foot muscles and suggests that there may be a fundamental difference in the contractile speed-twitch force relationship between many human muscles and most muscles of other mammals.

Segmental and supraspinal control of synaptic effectiveness of functionally identified muscle afferents in the cat.

The present investigation documents the patterns of primary afferent depolarization (PAD) of single, functionally identified muscle afferents from the medial gastrocnemius nerve in the intact, anesthetized cat. Classification of the impaled muscle afferents as from muscle spindles or from tendon organs was made according to several criteria, which comprised measurement of conduction velocity and electrical threshold of the peripheral axons, and the maximal frequency followed by the afferent fibers during vibration, as well as the changes in discharge frequency during longitudinal stretch, the projection of the afferent fiber to the motor pool, and, in unparalyzed preparations, the changes in afferent activity during a muscle twitch. In confirmation of a previous study, we found that most muscle spindle afferents (46.1-66.6%, depending on the combination of criteria utilized for receptor classification) had a type A PAD pattern. That is, they were depolarized by stimulation of group I fibers of the posterior biceps and semitendinosus (PBSt) nerve, but not by stimulation of cutaneous nerves (sural and superficial peroneus) or the bulbar reticular formation (RF), which in many cases inhibited the PBSt-induced PAD. In addition, we found a significant fraction of muscle spindle primaries that were depolarized by stimulation of group I PBSt fibers and also by stimulation of the bulbar RF. Stimulation of cutaneous nerves produced PAD in 9.1-31.2% of these fibers (type B PAD pattern) and no PAD in 8.2-15.4% (type C PAD pattern). In contrast to muscle spindle afferents, only the 7.7-15.4% of fibers from tendon organs had a type A PAD pattern, 23-46.1% had a type B and 50-61.5% a type C PAD pattern. These observations suggest that the neuronal circuitry involved in the control of the synaptic effectiveness of muscle spindles and tendon organs is subjected to excitatory as well as to inhibitory influences from cutaneous and reticulospinal fibers. As shown in the accompanying paper, the balance between excitation and inhibition is not fixed, but can be changed by crushing the afferent axons in the peripheral nerve and allowing subsequent reconnection of these afferent fibers with muscle receptors.

Serotonergic control of electric organ discharge in Gymnotus carapo. Role of 5-HT 2A/2c receptor subtypes

Resting frequency of the EOD and amplitude of the frequency changes induced by different stimulus modalities (novelty responses) were measured in Gymnotus carapo before and after pharmacological modulation of serotonergic transmission and in control groups. Stimulation of serotonergic transmission induced a decrease of resting frequency and the appearance of spontaneous frequency bursts. The amplitude of the transient change in discharge frequency induced by photic, acoustic, mechanical and electric stimuli was significantly enhanced after serotonergic stimulation. These effects were also produced by a selective ligand of 5-HT 2A/2c receptor subtypes. Selective blockade of the same receptors prevented the agonist effect and induced opposite changes, thus suggesting the existence of a tonic serotonergic control.

Basal ganglia motor control. II. Late pallidal timing relative to movement onset and inconsistent pallidal coding of movement parameters

1. We have tested the hypothesis that the basal ganglia initiate some one or several modes of movement by recording the change in discharge frequency of pallidal neurons during visually triggered step and visually paced ramp moves in relation to the visual stimulus onset, the change in the electromyograph (EMG), and the movement onset of trained rhesus monkeys. 2. The modal times of change for globus pallidus pars interna (GPi) were significantly later than those for forearm agonist muscle EMG. By contrast, the modal time of change for the cerebellar dentate nucleus preceded that for wrist agonist EMG. 3. The direction of change in discharge frequency of the GPi cells was for 71% an increase and for 29% a decrease. 4. Because of the relatively late change of activity of GPi neurons, we propose that GPi neurons cannot initiate these movements, as others have also suggested. The commands for the initiation of these movements may instead be generated by structures that include the lateral cerebellum and the anterior cerebral cortex. 5. We have also tested the hypothesis that the pallidum of the basal ganglia or the dentate of the lateral cerebellum may control the direction and other parameters of the trajectory by recording from both structures to see whether cell discharge correlated with the parameter and whether the correlation was consistent across tasks. Two rhesus monkeys were trained to perform hold-ramp-hold and hold-step-hold visually guided movements in opposite directions by flexing and extending the wrist with and against uniform oppositely directed torque loads (0.2 Nm). Wrist position, velocity, force, and EMG were recorded simultaneously. Movement amplitudes and directional intent were computed and inferred, respectively. 6. Task related neurons were classified as follows: 1) directional, if the discharge rate was reciprocal for opposite movements or if it increased or decreased during movement in one direction only; 2) bidirectional, if the discharge rate increased or decreased during movement in both directions; and 3) "other," if it was directional under one load and bidirectional under the other. During step tracking, 34 GPi, 47 globus pallidus pars externa (GPe), and 44 cerebellar dentate nuclear neurons were related to the task. Of the GPi cells, 14 (41%) were directional, 6 (18%) bidirectional, and 14 (41%) other. Of the GPe neurons, 13 (28%) were directional, 19 (40%) bidirectional, and 15 (32%) other. Of the dentate cerebellar nuclear cells, 5 (11%) were bidirectional, 31 (70%) bidirectional, and 8 (18%) other.(ABSTRACT TRUNCATED AT 400 WORDS)

Microiontophoresis of cocaine, desipramine, sulpiride, methysergide, and naloxone in habenula and parafasciculus

The effects of microiontophoretically applied cocaine, desipramine (DES), sulpiride (SUL), methysergide (METH), and naloxone (NAL) on the responses of physiologically identified single neurons in the habenula (Hab) and parafasciculus thalami nucleus (PF) were examined in rats. Three cell types were identified in both nuclei on the basis of the responses obtained following noxious stimulation that were classified as “nociceptive-on”, “nociceptive-off”, and “nonnociceptive” cells. Administration of cocaine generally resulted in a decrease in the firing rate of nociceptive-on and nonnociceptive neurons in both Hab and PF. In contrast, cocaine generally induced an excitation in the baseline firing of the nociceptive-off cells. Cocaine application concomitant with noxious stimulation prevented the evoked responses of the nociceptive-on and the nociceptive-off cells. DES, when applied alone, was found to induce excitation in neuronal discharge of all three cell types in both sites. Combined application of cocaine with DES resulted in no observable change in discharge frequency for the nociceptive-on and nonnociceptive cells, while inducing an additive excitatory effect on the nociceptive-off cells. SUL, in contrast, induced no observable effect on baseline firing when given alone, yet consistently antagonized cocaine-induced effects on all three cell types. Finally, METH and NAL induced no effects on baseline firing or cocaine-induced modifications in neuronal discharge frequency.

The influence of changes in discharge frequency of corticospinal neurones on hand muscles in the monkey.

1. The possibility that the discharge pattern of monkey corticomotoneuronal cells influences the degree to which they facilitate their target hand muscles was tested by compiling spike-triggered averages of EMG recorded from these muscles. 2. Records were made from area 4 corticomotoneuronal cells in three conscious macaque monkeys while they performed a precision grip between index finger and thumb. Simultaneous EMG recordings were made from up to six different intrinsic hand muscles. Twenty cells which produced clear post-spike facilitation of one or more muscles were selected for further analysis. 3. Spikes recorded from these cells were grouped according to the occurrence of a previous spike in the periods 0-10 ms, 10-20 ms, and so on up to 60-70 ms before the trigger spike. The post-spike period in which no additional spikes were allowed to fall was kept at either 12.5 or 25 ms. 4. Spikes selected in this way produced a transient facilitation of their target muscle EMG activity. The peak amplitude of this facilitation was normalized as a percentage of modulation of the background EMG level. The background level was determined from a period in the average to which the cell could not have contributed, because of the post-trigger spike interval. We verified that the percentage of modulation was not influenced by the overall level of EMG activity, since, for a given interval, the modulation was the same whether the relevant spikes were selected during periods of high- or low-level EMG activity. 5. The relative amplitude of the post-spike facilitation (i.e. the percentage of modulation) showed marked variation with interspike interval. A full analysis was completed for seventeen neurones. Spikes with the shortest intervals (less than 10 ms) usually produced the strongest effects, and evidence is presented that this was due to temporal summation and facilitation at the corticomotoneuronal synapse. Mid-range intervals (10-40 ms) were generally far less effective, although they constituted the highest proportion of cell activity. 6. A striking finding was the strong facilitation generated by the longer interspike intervals (40-70 ms). Although the absolute size of this post-spike effect was much smaller than that of the shortest intervals, its percentage of modulation was similar. It is suggested that this enhanced facilitation results from a combination of lower frequency discharge among the active motoneurones, and increased synchrony in the corticomotoneuronal input to them. 7. All of the above results were confirmed by examining cross-correlations between single corticomotoneuronal cells and single motor units in their target muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Muscular contraction stimulates posterior hypothalamic neurons.

Recent studies have suggested that the subthalamic locomotor region (STLR) of the posterior hypothalamus is involved in modulating cardiorespiratory responses to feedback from contracting muscles. The purpose of this study was to determine whether neurons in this hypothalamic region alter their discharge frequency during contraction of hindlimb muscles. Stainless steel electrodes were used to record single-unit activity of STLR neurons during static and rhythmic contractions of hindlimb muscles in anesthetized cats. Recordings were also made from neurons in areas outside but surrounding the subthalamic locomotor region. Contraction of the triceps surae muscles was induced by stimulation of the peripheral cut ends of the L7 and S1 ventral roots. Both static and rhythmic contractions of the triceps surae evoked an increase in the discharge rate of the majority of the STLR cells studied. Two types of excitatory responses were observed: 1) abrupt increases in discharge frequency at the onset of muscular contraction and 2) a delayed more gradual increase in firing. Most of the cells that responded to muscular contraction could be activated by mechanical probing of the triceps surae muscles. However, the changes in discharge frequency were unrelated to changes in arterial pressure occurring during muscular contraction. Most of the neurons located outside the STLR were slightly inhibited by or did not respond to muscular contraction. Thus input from contracting muscles exerts predominantly an excitatory effect on neurons in the posterior hypothalamus. These results are consistent with other studies which have concluded that this hypothalamic site is involved in influencing the cardiorespiratory responses to muscular contraction.

Sequential activation of neurons in primate motor cortex during unrestrained forelimb movement.

We trained monkeys to perform an unrestrained, reaching movement of the arm. Electromyogram (EMG) recordings of forelimb muscles revealed sequential activation, proximal to distal, of muscle groups involved in the task. The delay in onset of EMG activity between proximal (shoulder and elbow) and distal (wrist and finger) muscles was approximately 60 ms. We identified the neurons in the forelimb area of the contralateral motor cortex as controlling particular joints by previously defined criteria involving responses to somatosensory stimulation and effects of intracortical microstimulation. Many cells discharged prior to the onset of EMG activity acting on the appropriate joint, whereas others began firing at a later phase of the movement. The population of all proximal cells altered discharge patterns approximately 60 ms earlier than the population of distal cells. A small percentage of cells showed an initial inhibitory change in discharge frequency, and this inhibition typically occurred prior to the excitatory changes seen in the majority of cells. The results are discussed in terms of the "nested-zone" model of the forelimb motor cortex. The data support one of the predictions of this model, namely that discharges of identified cells within the cortical zones are causally related to voluntary movement at appropriate forelimb joints.

Visuomotor functions of central thalamus in monkey. II. Unit activity related to visual events, targeting, and fixation.

In alert monkeys, single-unit responses to visual stimuli were recorded in the central thalamic region where eye movement-related activity has been observed (33). Usually, the stimuli were 1 degree annulus patterns of dim light presented at unpredictable locations on a tangent screen. The animals were trained on two tasks: one in which they delivered the stimulus themselves by pressing a panel that they had to release immediately when the stimulus shape changed to a square, and another one in which the stimulus was turned on by the experimenter and the monkeys were rewarded for fixating this target for a predetermined length of time. In both tasks, continuous stimulus fixation was required. Receptive fields were tested with and without a fixation point. Retinal coordinates of stimuli were obtained by subtracting eye-position coordinates from stimulus coordinates in space, the monkey's head being fixed. Unit responses in the cases where targeting occurred or did not occur were analyzed separately. Transient responses were observed in 63 units and sustained responses in 44 units. Among the 63 units responding transiently, 42 did so irrespective of targeting. Their receptive fields were very large, generally including the fovea, and predominantly contralateral when the fields were asymmetric. The responses of the other 21 units depended on the occurrence of targeting. They were called visually triggered eye movement-related responses (VTEM). VTEM units were further subdivided in 9 units active only with targeting and 12 units showing the classical phenomenon of "response enhancement" under this condition. VTEM units were contrasted to six units that were both passively visually responsive and bursting with saccades, either spontaneous or visually triggered. The latencies of passive visual and VTEM responses to stimulus onset were comprised between 77 and 135 ms in 80% of the units. VTEM units also fired prior to retargeting saccades. Presaccadic units active with spontaneous saccades also discharged with visually elicited saccades. The earliest sign of activation after stimulus onset eliciting a saccade appeared between 80 and 100 ms, that is, in the same range of latencies as passive visual and VTEM units. Sustained visual responses consisted of activation in 18 units and inactivation in 26 units. The occurrence of these patterns of firing was related to stimulus fixation. In the majority of cases, the changes in discharge frequency started before fixation was achieved by a targeting saccade. They terminated before fixation was broken by a saccade away from the stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

Thermoreceptor localization in the deep and surface skin layers

1. 1.|Cold thermoreceptors of the back of the nose and the upper lip of rabbits were investigated. The receptors were influenced by temperature changes by means of surface and subcutaneous thermodes. The temperature of the thermodes was changed from 20 tp 40°C and back, at the rate of 2–3° s −1. 2. 2.|Seven out of ten cold receptors showed quick phasic changes in discharge frequency in response to temperature shifts of the surface thermode. The same temperature shifts in the subcutaneous thermode elicited, in these thermoreceptors, only slow gradual changes in discharge frequency. 3. 3.|The other three cold receptors showed slow gradual changes in discharge frequency in response to the temperature shifts in the surface thermode and quick phasic changes in response to the temperature shifts in the subcutaneous thermode. 4. 4.|On the basis of these data and temperature measurements in different skin layers the conclusion was drawn that part of cold receptors were located at a depth of 2.0–2.5 mm from the skin surface.

Mechanisms governing the relation between activity in the cerebral cortex and level of arousal.

1. It has been shown that the spontaneous activity of many neurons in the cerebral cortex changes whenever the animal’s level of arousal alters (A. C. Webb, Proc. R. Soc. Lond . B 194, 225–237, 239–251, 1976). It is generally agreed that the temporal pattern of discharge is sensitive to fluctuations in level of arousal. There is less agreement concerning effects on discharge frequency. 2. We have re-examined our own records of the spontaneous discharge of single cells in the visual, parietal and auditory cerebral cortex of unanaesthetized and unrestrained cats. We have also searched the literature for all comparable observations of single neurons in various cortical sites, recorded in the same and in other species. Most of the available data seem consistent with the idea that mean frequency of discharge of all mammalian cortical cells is affected in the same way by the transition from waking to slow-wave, or motionless sleep. 3. If the mean frequency of a cortical neuron when the animal is awake be W /s, and that of the same neuron in the sleeping animal be S /s, then the data from various cortical sites in cat and monkey can be fitted by a straight line: S = 2.00 + 0.45 W , correlation coefficient = 0.64. 4. The changes in discharge frequency that occur when an alarmed animal relaxes can also be fitted by a straight line. If the mean frequency of a cortical neuron when a cat is peacefully awake be W /s and that of the same cell when the cat is alarmed be A /s, then the relation between W and A can be described by W = 0.92 + 0.84 A , correlation coefficient = 0.92. 5. Neither excitation nor inhibition alone can account for the changes in spontaneous activity that accompany shifts in level of arousal. We propose a simple neural model that can account for the observed changes. This model assumes that, as level of arousal falls, the output of some subcortical system increases, providing both excitation and inhibition in fixed proportions.

Effects of ventral tegmental area stimulation and microiontophoretic application of dopamine and norepinephrine on hypothalamic neurons

The effects of ventral tegmental area of Tsai (VTA) stimulation on lateral hypothalamic (LH), lateral preoptic area (LPA), and medial hypothalamic neuronal activity were determined in anesthetized rats. Recordings from 81 hypothalamic neurons indicate that stimulation produces predominantly decreases in hypothalamic neuron activity. Increases in activity due to VTA stimulation occurred less frequently. Following single rectangular pulse stimulation, 0.5 msec, 0–500 μA, short latency decreases in activity occurred. Longer latency increases in discharge frequency were also observed. Dose response relations were established for 56% of the LH neurons, 78% of the LPA neurons, and for 82% of the medial hypothalamic neurons following VTA stimulation. Decreases and in a few cases increases in activity seemed to involve only one or two synapses. Antidromic responses verified interconnections between the VTA and the hypothalamus and revealed relatively slow conduction velocities of 0.45 and 0.81 m/sec. The changes in discharge frequency which occurred following VTA stimulation were similar in direction to the effects of the direct microiontophoretic application of dopamine (DA) or norepinephrine (NE). Since DA increased or decreased while NE decreased discharge frequency, these microiontophoretic tests indicated that the shorter latency VTA stimulation induced increases and decreases in neural activity were associated with VTA dopaminergic neuron stimulation and that in some cases short and long latency decreases in neuronal activity were due to activation of VTA ventral bundle NE fibers of passage or to indirect polysynaptic mechanisms. Results demonstrate the interconnections between various regions of the hypothalamus and the VTA along the extent of the medial forebrain bundle (MFB). The cross-validation of neuroanatomical and various electrophysiological metods in establishing the nature of hypothalamic connections was discussed.

Organization of single unit responses in the sensomotor cortex to combined stimulation of brain structures.

1. A temporary connection is formed, as reflected in single unit activity and evoked potentials (EPs) in the sensomotor cortex of waking, unimmobilized rabbits, during paired combination of stimulation of the medial lemnicus (ML), reticular tegmental nucleus (RF), and pyramidal tract (PT). The temporary connection is manifested in the dynamics of evoked responses and in changes in electrical activity in the place of usual application of the second stimulus when it is withheld. 2. In response to a combination of stimuli as indicated above the change in singleunit responses affects mainly the late components and occurs twice or three times more often than to simple repetition of the same stimulus. The dynamics of responses to combined stimuli is most clearly defined if the first stimulus consists of stimulation of RF or ML. On omission of the second stimulus, one-third of the neurons develop changes in discharge frequency, corresponding in time mainly to the late component of the response to the second stimulus. 3. Combined evoked potentials to a combination of stimuli undergo similar changes to those in single unit responses. On omission of the second stimulus a complex series of electrical waves consisting of elements of true reproduction of EP and waves outwardly differing in character from EPs to real stimuli develops in the place of its usual application in 75% of cases.

Statistical analysis of unit activity in the cat motor cortex

Activity of 366 neurons in the motor area of the biceps brachii muscle was studied in chronic experiments on cats during an instrumental placing response. Of these cells, 59 received afferentation from the skin, joints, or deep structures of the limb participating in movement. Of 160 neurons which changed their discharge during the placing response, 52 (32.5%) had a peripheral input. Three types of motor cortical neurons are described: I) changing their discharge frequency before movement began, II) after movement began, and III) before and during movement. Positive correlation (r=0.3926) was found between the presence of a peripheral input for the neurons studied and changes in discharge frequency during the placing response. Correlation between the presence of a concrete input in the neurons and the type to which they belonged was studied.

The activity of supplementary motor area neurons during a maintained precision grip

Two monkeys were trained to exert a precision grip of the thumb and forefinger and to maintain constant near-isometric force for a one-second duration. Both animals were trained to perform the task with about equal proficiency with either hand. A total of 134 neurons were recorded from the supplementary motor area (SMA) of the hemisphere contralateral to the performing hand. SMA neurons were identified by either the presence of peripheral fields on the contralateral arm or by consistent changes in discharge frequency during contralateral arm movement. Sixty-one cells demonstrated reliable changes in firing frequency during performance of the maintained precision grip. SMA neurons showed little tendency to discharge at higher frequency during force change rather than during maintained force. Only two neurons significantly increased firing frequency with increased finger force and no modulation of discharge related to rate of force change could be shown. The changes in spike frequency among SMA cells related to the arm were, on the average, about 100 msec after the onset of contraction in the forearm flexors and extensors of the wrist and fingers, although a contingent of cells discharging consistently before the onset of muscular activity was found.