Responses of motor cortex neurons of the cat to auditory stimulation and their role in the instrumental food reflex

The responses of motor cortex neurons in the cat to the presentation of a single auditory click and a series of 10 clicks presented with 1,000/sec frequency were studied under conditions of chronic experiments before and after the development of an instrumental food reflex. After reflex development a single presentation of a positive conditioned stimulus (single click) markedly influenced for 7 sec the appearance of instrumental movements. At the same time, the immediate responses of motor cortex neurons to presentation of the conditioned auditory stimulus had no impact on the appearance in the motor cortex of discharges leading to the realization of instrumental movements. Consequently, motor cortex neurons do not require activation from afferent sensory inputs for the generation of such discharges. The immediate neuronal responses to conditioned stimulation did not inhibit the realization of the instrumental reflex. It is proposed that they are associated with the realization of motor function in the unconditioned defensive response evoked by the presentation of an auditory stimulus. The presence or absence of responses to auditory conditioned stimulation was dependent upon the signal meaning of the stimulus, its physical parameters, and the degree of excitability of the animal.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 539–550, July–August, 1985.     

Neuron activities of the motor cortex during conditioned eye blink reflex in rabbits (author's transl)]

Effects of the tone (CS) on neurons of the motor cortex were investigated in naive, pseudoconditioned, and conditioned rabbits. Conditioning to eye blink reflex was made by a combination of CS and air puff (US). Effects of electrical stimulation of the subcortical structures were also observed on the cortical neurons associated with the conditioned reflex. The results were as follows. (1) Proportion of neurons which significantly increased the firing rate in response to the CS, type E, was higher in the conditioned group than in other two groups. On the other hand, no group difference was found in the proportion of neurons which significantly decreased the firing rate to the stimulus, type I. (2) Most of the type E neurons in the conditioned rabbits began to fire at latencies of about 50 to 100 msec after the CS, preceding about 200 msec to the appearance of the peripheral conditioned responses (EMG). (3) Most of the type E neurons in the conditioned animals were more easily affected by stimulation of the medial geniculate body and the brain stem reticular formation. Based on the results mentioned above, it is concluded that in the rabbits conditioned to the eye blink reflex, excitability of neurons in the motor cortex is enhanced by the tone (CS), and by electrical stimulation to the medial geniculate body and the brain stem reticular formation.     

Electrophysiological analysis of facial reflex in monkeys: trigemino-naso-labial reflex]

Electrical stimulation of the awake monkey's supra orbital nerve, elicits two successive reflex discharge in both naso-labialis muscles (NL). The responses have a similar high threshold. Similar responses are also elicited on electrical stimulation of the facial skin, whereas flash, click or tapping on the muscle belly are ineffective. These responses bear some resemblances to those obtained in orbicularis oculi muscles ; but the higher threshold and the different organization of the NL responses would suggest that such reflexes may serve a different function from that of the blink reflex.     

A computer model of generation of the motor cortex neuron processes seen in the course of execution of instrumental movement

A computer model of neuronal processes in the motor cortex column is presented. The model is consisted of two pyramidal cell layers with two groups of inhibitory interneurons, selectively controlling pyramidal cell soma and dendrite, in each. Active Na, Ca and K conductances are included in the model of a single neuron. Horizontal excitatory connections between pyramidal cells in the upper layer are largely of NMDA-receptor type, that in the lower layer--of non-NMDA-type. All inhibitory synapses are of GABA(A)-type. The model reproduces the main phenomenon observed in the motor cortex during the execution of conditioned movements. Consequent to an early excitation the upper layer pyramidal cells generate a late NMDA-dependent reflexive response to afferent conditional stimulation, which as in a real case is diminished by GABA(A)-type synaptic inhibition and afferent stimulus strength increase. The characteristic inverse relation between the late response manifestation and the stimulus strength observed in the real cortex can be reproduced in the model only if NMDA-glutamate receptors were preferentially localized in the terminals of pyramidal cell backward collaterals, not in the terminals of the afferent fibers on pyramidal neurons. The intended component of motor cortex neuronal activity is generated in NMDA-independent manner by the pyramidal cells of lower layer. The slow time coarse of intended component as compared with short duration of AMPA epsp's is due to a consecutive relay-race--like activation of pyramidal neurons with different dendrit-to-soma ratio.     

Activation of glutamate ionotropic connections of sensorimotor cortex neurons during conditioning

Changes in conditioned impulse reactions of neurons in sensorimotor cortex were studied during microiontophoretic application of glutamatergic and GABA ergic agonistic and antagonistic drugs. It was shown that ionotropic glutamate receptors (AMPA and NMDA) are activated by a conditioned stimulus. Not only large pyramidal neurons of deep cortical layers but surrounding short-axon inhibitory interneurons are involved in the reaction. It was shown that the activity of pyramidal neurons is under a constant inhibitory control from surrounding interneurons. This inhibition is involved in organization of excitatory cortical responses during conditioning.     

Relative contributions of eyelid and eye-retraction motor systems to reflex and classically conditioned blink responses in the rabbit.

Early compensatory mechanisms between eyelid and eye-retraction motor systems following selective nerve and/or muscle lesions were studied in behaving rabbits. Reflex and conditioned eyelid responses were recorded in 1). controls and following 2). facial nerve section, 3). retractor bulbi muscle removal, and 4). facial nerve section and retractor bulbi muscle removal. Animals were classically conditioned with a delay paradigm by using a tone (350 ms, 600 Hz, 90 dB) as conditioned stimulus, followed 250 ms later by an air puff (100 ms, 3 kg/cm(2)) as unconditioned stimulus. Conditioned eyelid responses generated in the absence of the facial motor system (i.e., by the almost sole action of the retractor bulbi motor system) presented a wavy profile, due to the succession of eye-retraction movements. Learned eyelid responses generated in the absence of the eye-retraction motor system (i.e., by the almost exclusive action of the facial motor system) were similar to those of controls, but were reduced in amplitude and peak velocity. Finally, the isolated action of the extraocular recti muscle produced very small eyelid movements during both reflex and learned eyelid responses. Although each of these motor systems could act independently of the others, the motor result of their joint action did not coincide with the simple addition of their separate actions. Both facial and eye-retraction motor systems appear to be necessary for normal eyelid closure during blinking in rabbits. Central reorganization to compensate for loss of either of these systems may explain why the response of each system in isolation cannot be added linearly to obtain normal blink response magnitudes and profiles.     

Neural mechanisms of classical conditioning in mammals

Evidence supports the view that 'memory traces' are formed in the hippocampus and in the cerebellum in classical conditioning of discrete behavioural responses. In the hippocampus learning results in long-lasting increases in excitability of pyramidal neurons that resemble the phenomenon of long-term potentiation. Although it plays a role in certain aspects of conditioning, the hippocampus is not necessary for learning and memory of the basic conditioned responses. The cerebellum and its associated brain-stem circuitry, on the other hand, does appear to be essential (necessary and sufficient) for learning and memory of the conditioned response. Evidence to date supports the view that mossy fibre convey conditioned stimulus information and that climbing fibres conveys the critical 'reinforcement' information to the cerebellum and that 'memory traces' appear to be formed in cerebellar cortex and interpositus nucleus.     

Instrumentalization of movements induced by stimulation of motor cortex with food reinforcement in dogs

Contrary to some literature data, the possibility to instrumentalize the movements (liftings) of the hind limb elicited by stimulation of the corresponding contralateral area of the motor cortex was shown. The instrumental reflex (spontaneous high lifting of the hind limb) was acquired after a number of uniform trials: cortical stimulation--movement--food. Food delivery was preceded by a click, which was presented during the hind limb lifting and served as a secondary reinforcement. The acquisition was rather prolonged (50-200 trials) and demanded some special conditions. The results count in favor of the viewpoint that the motor cortex can directly participate in establishing the instrumental conditioned connection (motivation--movement), and simple instrumental movements can be initiated through this connection.     

Neurophysiological analysis of efferent-afferent interaction of neurons of the parietal associate cortex in cats

Neuronal responses of the parietal associate cortex (field 5) was recorded in waking cat during electrical stimulation of the pyramidal tract axons and afferent stimulation. The electrical stimulation of the pyramid evoked marked responses in 39% of neurons. 87% of these neurons increased spike activity during sematic nociceptive stimulation, 61% of test neurons were activated by light or tonal stimulation. Neuronal activity was recorded during defensive conditioning to the pyramidal tract axons stimulation. It has been shown that conditioned stimulation of the pyramidal tract evoked plastic changes of responses in 66% of neurons of the parietal cortex. These data are discussed relative to the possible functional role of the efferent-afferent interaction to field 5.     

A glimpse of the brain transforming a sensory signal into a motor response

Averages were made of neuronal spike activity recorded successively from eight relay regions along the auditorimotor pathway of naive cats and cats conditioned to blink in response to a 70 dB click conditioned stimulus (CS). It was hypothesized that the patterns of activity could be distinguished as sensory or motor by differences in their relationship to the pattern of the acoustic CS vs that of the conditioned response (CR). If so, it was also hypothesized that the acoustic stimulus would be better expressed at early auditorimotor relays and the motor response at later relays along the pathway. To test these hypotheses, Pearson correlation coefficients were calculated between the mean patterns of unit activity at each of the auditorimotor relays and (1) the rectified sound pattern of the CS and (2) the averaged, rectified electromyographic (EMG) activity of the muscles (orbicularis oculis) that produced the CR. In both naive and conditioned cats, there were significant positive correlations between the patterns of spike activity and the sound at early relays along the auditorimotor pathway such as the cochlear nucleus and inferior colliculus. In the conditioned animals, the spike activity of later nuclei in the auditorimotor pathway, such as the rostral thalamus and the motor cortex, had the highest positive correlations with the motor response. These correlations were low in the naive animals. Thus, the mean patterns of spike activity along the auditorimotor pathway appeared to distinguish the sound from the motor response and provided a glimpse of the process supporting transformation of the CS into the incipient CR.     

A glimpse of the brain transforming a sensory signal into a motor response

Averages were made of neuronal spike activity recorded successively from eight relay regions along the auditorimotor pathway of naive cats and cats conditioned to blink in response to a 70 dB click conditioned stimulus (CS). It was hypothesized that the patterns of activity could be distinguished as sensory or motor by differences in their relationship to the pattern of the acoustic CS vs that of the conditioned response (CR). If so, it was also hypothesized that the acoustic stimulus would be better expressed at early auditorimotor relays and the motor response at later relays along the pathway. To test these hypotheses, Pearson correlation coefficients were calculated between the mean patterns of unit activity at each of the auditorimotor relays and (1) the rectified sound pattern of the CS and (2) the averaged, rectified electromyographic (EMG) activity of the muscles (orbicularis oculis) that produced the CR. In both naive and conditioned cats, there were significant positive correlations between the patterns of spike activity and the sound at early relays along the auditorimotor pathway such as the cochlear nucleus and inferior colliculus. In the conditioned animals, the spike activity of later nuclei in the auditorimotor pathway, such as the rostral thalamus and the motor cortex, had the highest positive correlations with the motor response. These correlations were low in the naive animals. Thus, the mean patterns of spike activity along the auditorimotor pathway appeared to distinguish the sound from the motor response and provided a glimpse of the process supporting transformation of the CS into the incipient CR.     

NMDA-dependent and NMDA-independent neuronal processes in the cat motor cortex,disinhibited by bicuculline,during forepaw placement conditioning

Neuronal activity associated with a conditioned forepaw placing reaction was recorded in the cat's motor cortex locally disinhibited by bicuculline spontaneously diffused from the recording pipette. Electrical stimulation of the parieral cortex (area 5) with 3-5 pulses was used as a conditioned stimulus. In both naive and trained cats, adding of APV (NMDA receptor blocker) led to disappearance of the late (30-120 ms) secondary excitatory responses from the pattern of the neuronal reaction to the parietal stimulation recorded in the motor cortex. At the same time, the APV administration did not change the excitatory reactions (recorded, predominantly, in the deep cortical layers) time-locked to the execution of the conditioned movement. The conditioning resulted in a statistically significant increase in the amplitude and duration of the late secondary responses as well as in a shortening of their latency. In some cases (after a long period of training), the late secondary responses to the conditioned stimulus transformed into paroxysmal epileptiform bursts. A hypothesis is discussed that the increase in synaptic strength of the backward horizontal collaterals of layer-II/III pyramidal neurons is responsible for the learning-related changes in the neuronal reactions in the disinhibited motor cortex.     

Role of Acetylcholine in the Modulation of Activity of Neocortical Neurons in Awake Animals Performing an Instrumental Conditioned Reflex

We studied modulatory effects of the cholinergic system on the activity of sensorimotor cortex neurons related to realization of an instrumental conditioned placing reflex. Experiments were carried out on awake cats; multibarrel glass microelectrodes were used for extracellular recording of impulse activity of neurons in the sensorimotor cortex and iontophoretic application of synaptically active agents within the recording region. The background and reflex-related activity was recorded in the course of realization of conditioned movements, and then changes of spiking induced by applications of the testing substances were examined. Applications of acetylcholine and carbachol resulted in increases in the intensity of impulse reactions of neocortical neurons evoked by presentation of an acoustic signal and in simultaneous shortening of the response latencies. An agonist of muscarinic receptors, pylocarpine, exerted a similar effect on the evoked activity of sensorimotor cortex neurons. Blockers of muscarinic receptors, atropine and scopolamine, vice versa, sharply suppressed impulse reactions of cortical neurons to afferent stimulation and simultaneously increased latencies of these responses. Applications of an agonist of nicotinic receptors, nicotine, was accompanied by suppression of impulse neuronal responses, an increase in the latency of spike reactions to presentation of a sound signal, and a corresponding increase in the latency of a conditioned motor reaction. In contrast, application of an antagonist of nicotinic receptors, tubocurarine, significantly intensified neuronal spike responses and shortened their latency. The mechanisms underlying the effects of antagonists of membrane muscarinic and nicotinic cholinoreceptors and the role of activation of these receptors in the modulation of activity of pyramidal and non-pyramidal neocortical neurons related to realization of the instrumental motor reflex are discussed.     

Comparison of neuronal response pattern in the rat somatosensory cortex during active and passive vibrissae movements

A comparative study of neuronal response in separate cortical columns of the somatosensory cortex (the barrel field area) was made in unanesthetized partially curarized white rats under various circumstances: during passive deflection of immobile vibrissa, unhindered volitional sweeping movement of the vibrissae, and during movement induced by stimulating the motor cortex and facial muscles. Differences in the response of the same neurons emerged under these different experimental situations. Different groups of neurons — responding before, during, and after volitional vibrissa movements were observed. Such response is thought to be triggered by different afferent trains reaching cortical column neurons from sources including the motor cortex, the vibrissa follicle receptors, and facial muscles.Institute of Neurocybernetics, State University, Rostov-on-Don. State University, Simferopol. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 235–242, March–April, 1990.     

Movement as a signal during classical conditioning

Analysis of the available data and that of the author disclosed the peculiarities of motor reaction when used as a conditioned stimulus. The author's data showed that if signal value is attributed to a motor reaction (passive movement or movement evoked by the direct stimulation of the motor cortex), the changes of excitability in the motor cortex representation of the dog's leg depend on the biological sign of the reinforcing stimulus during classic conditioning. They also remained the same during instrumental conditioning and were opposite in sign, showed increased excitability in the food situation, and decreased excitability in the defense situation. Using the movement as a conditional stimulus, we managed to uncover the commonality between classic and instrumental conditioning. This enabled us to answer questions, discussed by Pavlov and Guthrie, which, it seems to us, had not been convincingly answered during their time.     

The modulation of the pulse activity of neocortical neurons during a conditioned reflex]

Spontaneous and evoked activity of neurons in the sensorimotor cortex was recorded in cats with learned conditioned placing reaction before, during, and after the iontophoretic application of synaptically active substances. It was shown that apart from direct excitatory effect on the cortical neurons during its application, glutamate (Glu) exerted some modulatory influence on unit activity in subsequent 20 min. Noradrenaline suppressed the background and evoked activity through beta 1 adrenoreceptors. Activation of beta 2 adrenoreceptors by metaproterenol was accompanied by facilitation of the background and evoked activity during application and 10-20 min after. The joint application of Glu and metaproterenol improved facilitation of neuronal responses evoked by conditioned stimuli. Application of levodopa, like Glu, increased the background and evoked activity of many sensorimotor cortical neurons. The joint effect of Glu and levodopa was not substantially more intensive than the changes produced by the isolated application of any of these substances. A nonselective blocker of DA1 and DA2 receptors haloperidol either increased or did not change the background and evoked activity of some cortical neurons. In contrast to isolated application of Glu, simultaneous application of Glu and haloperidol to neocortex suppressed the neuronal responses associated with conditioned movements. The results suggest that the Glu-induced potentiation is substantially realized through molecular mechanisms common for Glu and dopamine, probably, through Gi-proteins. The conclusion is drawn that the adrenergic and dopaminergic inputs to neocortical neurons are involved in the Glu-mediated plastic changes in the cortex during conditioning.     

Does the supplementary motor area play a part in modifying motor cortex reflexes?

Neuronal activity in the supplementary motor area was recorded from a monkey performing a trained motor task that required readiness for proper usage of sensory inputs. Thirty-two neurons exhibited activity changes, which supports the hypothesis that the SMA is part of the system involved in modulating responsiveness of the motor cortex to sensory inputs in association with learned movements.     

Effect of the microiontophoretic application of acetylcholine on the formation of conditioned reactions in motor cortex neurons

In alert rabbits the activity of the motor cortex neurones was recorded with simultaneous application of acetylcholine to them in the process of defensive conditioning. Conditioned reorganization, mainly of activation type, were found in 60% of neurones. In most cases conditionally reacting cells were sensitive to acetylcholine. Ionophoretic application of the transmitter promoted the formation of conditioned neuronal responses and increased them in comparison with conditioned reactions evoked in absence of acetylcholine. It is supposed that the influence of acetylcholine on conditioned cellular process is realized due to its action on the state of excitability of the cortical neurones.     

Magnetic stimulation of the human motor cortex evokes skin sympathetic nerve activity.

Single-pulse magnetic coil stimulation (Cadwell MES 10) over the cranium induces without pain an electric pulse in the underlying cerebral cortex. Stimulation over the motor cortex can elicit a muscle twitch. In 10 subjects, we tested whether motor cortical stimulation could also elicit skin sympathetic nerve activity (SSNA; n = 8) and muscle sympathetic nerve activity (MSNA; n = 5) in the peroneal nerve. Focal motor cortical stimulation predictably elicited bursts of SSNA but not MSNA; with successive stimuli, the SSNA responses did not readily extinguish (94% of discharges to the motor cortex evoked SSNA responses) and had predictable latencies [739 +/- 33 (SE) to 895 +/- 13 ms]. The SSNA responses were similar after stimulation of dominant and nondominant sides. Focal stimulation posterior to the motor cortex elicited extinguishable SSNA responses. In three of six subjects, anterior cortical stimulation evoked SSNA responses similar to those seen with motor cortex stimulation but without detectable movement; in the other subjects, anterior stimulation evoked less SSNA discharge than that seen with motor cortex stimulation. Contrasting with motor cortical stimulation, evoked SSNA responses were more readily extinguished with 1) peripheral stimulation that directly elicited forearm muscle activation accompanied by electromyograms similar to those with motor cortical stimulation; 2) auditory stimulation by the click of the energized coil when off the head; and 3) in preliminary experiments, finger afferent stimulation sufficient to cause tingling. Our findings are consistent with the hypothesis that motor cortex stimulation can cause activation of both alpha-motoneurons and SSNA.