Responses of the neurons of the parietal associative cortex of the cat brain to indifferent and conditioned acoustic stimuli

Neuronal responses of the associative cortex (field 5) to indifferent and to conditioned sound stimuli were studied. The number of neurons responding to the conditioned sound during classical reflex increased two times. A percentage of inhibitory responses of neurons to conditioned acoustic stimulus during placing reflex grew. Neurons were found which responded to the conditioned sound only in the absence of the conditioned movement during instrumental food reflex. Despite the fact that the associative cortex participates in the analysis of sensory signals and in evaluation of their biological significance, its main functional property is its involvement in the initiation of behavioral reaction to the conditioned stimulus.     

The activity of visual cortex neurons during alimentary and defensive behavior]

The reactions of the rabbit visual cortex neurons in response to conditioned light flashes were investigated during the process of repeated changes of the feeding behaviour to the avoidance one. It is demonstrated that one and the same flash evokes different responses of the same neuron while triggering different behaviour.     

Responses of neurons in the SI zone during a defensive conditioned reflex to sound]

Responses of single neurons in the primary projection zone of the somatosensory cortex to conditioned and electrocutaneous reinforcing stimuli were investigated in chronic experiments on cats with a preliminary developed sound conditioned defensive reflex. Five types of neuronal responses to reinforcing stimulus during application of combination were separated; such differentiation was impossible for neuronal responses appearing in the place of the absent reinforcing stimulus. A comparison of neuronal spike activity with the conditioned movement reaction revealed strict correlation between these processes. The conditioned movement reaction usually preceeded the conditioned neuronal response.     

Participation of neurons of the midbrain reticular formation of the cat in conditioned reflex activity

Spike discharges of mesencephalic reticular formation neurons were investigated during classical and instrumental conditional reflexes in chronic experiments on cats. Neurons were divided into several functional groups according to patterns of their responses. Two groups of neurons produced continuous tonic spike discharges. One of them was activated by positive conditional stimuli and did not respond to the same stimulus after extinction. Another group was involved in reaction only after extinction. Thus the neurons of these two groups developed additional tonic ascending action not only during fulfillment of conditional reflex but under its internal inhibition too. Neurons of the third group revealed double phasic responses: the first--to sound and the second--in connection with initiation of the conditioned movement. They decreased the level of the background and evoked activity during differentiation and extinction. Initial changes of reticular neuron responses were similar under conditioning and under pseudoconditioning. It is concluded that mesencephalic reticular formation takes an active and differential participation in elaboration, fulfillment and internal inhibition of classical and instrumental conditional reflexes.     

Characteristics of the neuronal responses of the auditory zone of the cortex of awake cats in the resting state and during an elaborated defensive conditioned reflex]

The responses of 288 neurons with background activity in the first auditory cortex were investigated using glass microelectrodes in chronic experiments on cats at rest (123 neurons) and during elaboration of a defensive conditioned reflex to sound stimulation (165 neurons). At rest 43% of recorded neurons did not respond to the sound stimulus. Pronounced inhibition of background activity prevailed among responding neurons (about 60%). The conditioning caused an increase (to 72%) in proportion of neurons responsive to the sound stimulus, appearance of tonic reactions, as well as an increase in frequency of bursts and in proportion of activation type responses. It is suggested that these changes indicate the enhancement of neurons excitability in the zone under study during conditioning.     

Cortically projecting cells in the periaqueductal gray matter of the rat. A retrograde fluorescent tracer study

The topographical organization of the afferent input from the periaqueductal gray matter (PAG) to the cerebral cortex has been assessed in rats by retrograde transport of the fluorescent tracers Fast blue (FB) and Diamidino yellow (DY). The olfactory, medial frontal (infralimbic, prelimbic and anterior cingulate cortices), lateral frontal (motor), parietal, temporal, occipital and insular cortices were explored by placing two fluorescent tracers into two different cortical regions. The PAG contained the largest number of labeled neurons in medial frontal cortex injections, followed by olfactory and lateral frontal cortices. Fewer retrogradely labeled cells were seen after injections in parietal, temporal occipital and insular cortices. All labeled cells were exclusively located in the medial and lateroventral divisions of the PAG (PAGm and PAGlv). The longitudinal extent of the labeling in PAGm was more extensive than in PAGlv. The labeled neurons in the medial frontal cortex group extended through most of the PAG, while in the remaining groups it was restricted to the caudal one-third of the PAG. Neurons with projections to two different cortical regions were only a small fraction of the total population of labeled cells. Our data indicate that the medial frontal cortex is the most important recipient of a direct PAG input, followed by the lateral frontal cortex. Parietal, temporal, occipital and insular cortices receive only a minor projection. It is concluded that the PAG sends direct projections over the majority of the cortical mantle. Therefore, the possibility arises that the cerebral cortex receives a direct influence from the brainstem without a thalamic relay.     

Activity of neurons of the motor cortex of the cat during inhibition of a postural change conditioned reflex

Spike reactions were recorded from motor cortex neurons in cats in the forelimb projection area during external and internal inhibition of the conditioned postural adjustment (transfer of the body weight) of the same limb. Spike responses evoked by external stimulation were of the same character as the responses during conditioned stimulation. As a rule, they were determined by the state of the animal and its habituation to the applied stimulus. Duration of the responses during external stimulation was shorter in trained cats than in untrained ones. Late after-discharges of units and associated conditioned movements disappeared simultaneously during external and internal inhibition. Sometimes the external stimuli were able to depress after-discharges even when the conditioned movements appeared. External stimuli of various modalities inhibited the reflex in different manners. The changes of spike reactions during conditioned posture adjustment resembled those during well learned local conditioned events.     

Tonal response patterns of primary auditory cortex neurons in alert cats

The firing rates of primary auditory cortex (A1) neurons are known to be modulated only at the onset, offset, and change of a tonal stimulus in anesthetized animals. The tonal response pattern has been rarely investigated in alert animals. We investigated the time-course of A1 neuron responses to a steady tonal stimulus in alert cats. We found four types of firing responses based on statistical evaluation of the time course of the firing rate. The tonic cells (38 cells) showed a significant (P<0.05) firing increase throughout the stimulus period after a relatively long latency (mean, 25.3 ms) with little tendency of adaptation. The phasic-tonic cells (22 cells) showed a significant firing increase throughout the stimulus period after a medium latency (19.8 ms) with tendency of adaptation to less than a half of the maximum excitation level. Phasic cells (15 cells) responded, after a short latency (10.2 ms), at onset and offset of the stimuli. The unresponsive cells (26 cells) did not show a significant firing increase during stimuli. The findings suggest that there is a functional difference between each type of cells: the tonic cells encode information of static auditory signals in their firing rates; the phasic-tonic cells, of the changing auditory signal during the stimulus period; and the phasic cells, of rapid change of the auditory signal at onset and offset.     

Ethanol withdrawal results in aberrant membrane properties and synaptic responses in periaqueductal gray neurons associated with seizure susceptibility

The midbrain periaqueductal gray (PAG) is implicated as a component of the neuronal network for ethanol withdrawal (ETX) seizures and in other forms of audiogenic seizure (AGS) in rats. Previous in vivo experiments suggest that neurons in the ventrolateral PAG (VL PAG) are required for generation of the clonic and tonic seizure behaviors of AGS. During these seizures, PAG neuronal firing rates increase markedly, but the intracellular events, contributing to this phenomenon, have not been characterized. In the present in vitro study, intracellular current-clamp recordings were obtained from 115 control VL PAG neurons and 71 neurons during ETX. The amount of depolarizing current that needed to be injected into ETX neurons in order to generate an action potential (AP) (N=40) was significantly less than control (N=52). ETX also yielded a significant leftward shift in the frequency-current curve of VL PAG neurons. VL PAG neurons during ETX had significantly enhanced spike firing tendencies, but the firing pattern was similar in ETX and control. ETX significantly increased the incidence of spontaneous APs and the frequency of firing above those in control. A number of cellular properties [e.g. resting membrane potential (RMP), amplitude of AP, AP width at half-height, input resistance and time constant] did not differ significantly between ETX and control neurons. The current-voltage (I-V) relationships of the ETX and control VL PAG neurons were nearly linear between RMP and 80 mV more negative than RMP, whereas the I-V relation was non-linear beyond this range. Stimulation in the dorsolateral PAG in either ETX or control neurons evoked a fast excitatory postsynaptic potential (EPSP) and a slow inhibitory postsynaptic potential (IPSP). The stimulus intensities required to evoke EPSPs were significantly lower than control in neurons during ETX. Epileptiform firing was observed commonly (20%) during ETX but was never seen in control rats. Paired-pulse responses evoked paired-pulse inhibition in approximately 80% of VL PAG neurons from control rats (N=38), which was significantly above the incidence (12%) of this pattern during ETX (N=25). Paired-pulse facilitation was significantly more common (88%) in VL PAG neurons (N=25) during ETX compared to approximately 20% in controls (N=38). These aberrant membrane and synaptic properties provide direct evidence regarding the basis of the hyperexcitability observed in VL PAG neurons in vivo that contribute to propagation mechanisms of clonic and tonic convulsions, occurring during ETX.     

Discharge patterns of pallidal neurons with input from various cortical areas during movement in the monkey

Activities of pallidal neurons were studied in awake monkeys which were implanted with stimulating electrodes in the various cortical areas in the frontal lobe. Cortical inputs to each pallidal neuron were examined by inhibitory responses to stimulation through these electrodes. Discharge patterns of pallidal neurons were observed during performance of the reaction-time, delayed go/no-go discrimination and self-paced movement tasks. Most of the pallidal neurons with input from the arm of the motor cortex changed their firing rate in close relation to the arm movement (movement-related activity). Many of the neurons with input from the supplementary motor and cingulate areas showed sustained changes in discharge rate during the delay period in addition to movement-related activity. Most of the neurons with input from prefrontal cortex responded to light stimulus.     

Prefrontal cortex neuron activity during a discriminative conditioning paradigm in unanesthetized rats

Single neuron responses were recorded from the prefrontal cortex of unanesthetized, restrained rats trained to a discriminative conditioning paradigm. The animals were preconditioned to a tone paired with footshock (CS+) and a second tone presented unpaired (CS-). Only neurons with large amplitude, positive first deflection action potentials were studied. Eighty-five percent of the units (17 of 20) emitted conditioned responses in that the response to either one or both of the conditioned stimuli (CS) was significantly different from spontaneous activity. Thirty-five percent of the units emitted differential conditioned responses in that the responses to one of the CS was significantly different than the response to the other CS and that the response was subsequently shown to extinguish when the footshock was withheld. The neurons which emitted the differential conditioned responses appeared to be located in the deeper layers of the anteromedial prefrontal cortex while the remaining neurons were located either in more superficial layers or anterior aspects of the prefrontal cortex. The results suggest that the anteromedial prefrontal cortex may be involved in neural mechanisms related to discriminative conditioning.     

Nucleus basalis involvement in conditioned neuronal responses in the rat frontal cortex

Rat frontal cortex neurons exhibit alterations in firing in response to a 2 sec tone cue followed by rewarding medial forebrain bundle (MFB) stimulation. Nucleus basalis neurons supply up to 75% of the cortical cholinergic innervation. The nucleus basalis and ACh have been implicated as playing a role in cognitive function. Three experiments were designed to test the hypothesis that the nucleus basalis cholinergic system is involved in the generation of conditioned neuronal responses in the rat frontal cortex. Local microinjection of the cholinergic antagonist, atropine, into the frontal cortex suppressed the conditioned responses of 22 of 25 cortical single units. Unilateral kainic acid lesioning of the nucleus basalis resulted in a significant decrease in the proportion of units exhibiting conditioned responses in the cortex ipsilateral to the lesion (25%) compared to the proportion of responding units from the cortex of untreated animals (70%). When the firing rates of units encountered in the region of the nucleus basalis were monitored during presentation of the cue-MFB paradigm, 28 of 38 unit recordings exhibited significant increases or decreases in firing rate. Therefore, the results of the experiments indicate that the nucleus basalis cholinergic neurons are involved in the generation of conditioned neuronal responses in the rat frontal cortex.     

Differential responsivity of neurons in perirhinal cortex,lateral entorhinal cortex,and dentate gyrus during time‐bridging learning

Many studies have focused on the function of hippocampal region CA1 as a critical site for associative memory, but much less is known about changes in the afferents to CA1. Here we report the activity of multiple single neurons from perirhinal and entorhinal cortex and from dentate gyrus during trace eyeblink conditioning as well as consolidated recall, and in pseudo‐conditioned control rabbits. We also report an analysis of theta activity filtered from the local field potential (LFP). Our results show early associative changes in single‐neuron firing rate as well as theta oscillations in lateral entorhinal cortex (EC) and dentate gyrus (DG), and increases in the number of responsive neurons in perirhinal cortex. In both EC and DG, a subset of neurons from conditioned animals exhibited an elevated baseline firing rate and large responses to the conditioned stimulus and trace period. A similar population of cells has been seen in DG and in medial, but not lateral, EC during spatial tasks, suggesting that lateral EC contains cells responsive to a temporal associative task. In contrast to recent studies in our laboratory that found significant CA1 contributions to long‐term memory, the activity profiles of neurons within EC and DG were similar for conditioned and pseudoconditioned rabbits during post‐consolidation sessions. Collectively these results demonstrate that individual subregions of medial temporal lobe differentially support new and remotely acquired memories. Neuron firing profiles were similar on training trials when conditioned responses were and were not exhibited, demonstrating that these temporal lobe regions represent the CS–US association and do not control the behavioral response. The analysis of theta activity revealed that theta power was modulated by the conditioning stimuli in both the conditioned and pseudoconditioned groups and that although both groups exhibited a resetting of phase to the corneal airpuff, only the conditioned group exhibited a resetting of phase to the whisker conditioned stimulus.     

A role for acetylcholine in conditioning-related responses of rat frontal cortex neurons: microiontophoretic evidence

In an associative conditioning paradigm, an auditory stimulus (CS+) was paired with rewarding medial forebrain bundle stimulation or a tone of different frequency (CS-) was presented without pairing. After training, slow potential (SP) and single neuron responses were recorded from rat frontal cortex. When cortical SP responses indicated the development of discrimination between CS+ and CS- tones, single neurons could be isolated that exhibited a discriminative response to CS+. Seventy-three percent of the 56 neurons which discriminated between CS+ and CS- were excited by the paired tone while the remainder were inhibited. Iontophoretically applied acetylcholine increased spontaneous firing rate in 90% of the excited cells and 87% of the inhibited cells. Iontophoretic administration of a muscarinic receptor antagonist, either atropine or tropicamide, during trial presentation attenuated the conditioning-related response to CS+ as well as the response to acetylcholine in the majority of neurons. The largest group of discriminating neurons were excited by both CS+ and acetylcholine, and both responses were suppressed by the antagonists. The results provide evidence that conditioning-related responses of a major population of frontal cortex neurons are modulated by cholinergic input, a portion of which may originate in the basal forebrain area. There also may be a significant non-cholinergic influence on these neuronal responses.     

The interaction of neurons characterized by a tonic reaction to sound with other neurons in the cat auditory cortex

Interaction of neurons with tonic response to sound with adjacent or distant (approximately 400-500 micrograms) cortex neurons was studied in acute experiments on 15 immobilized cats using a method of the cross-correlation analysis. A presence of synchronizing excitatory input common for the cells has been revealed in 26 pairs (72%) on the cross-correlograms. The results of the cross-correlation analysis in five pairs of neurons show mono- or polysynaptic excitatory effect of a tonic neuron to impulse activity of another neuron. Negative correlation indicative of the inhibitory influence of tonic neurons on impulse responses of other neurons of the same or adjacent auditory cortex column is revealed in five pairs of neurons, but the inhibitory influences may be considered as monosynaptic ones only in 3 pairs of these neurons (latency of interaction 1.0-1.5 ms). The data obtained permit concluding that the group of neurons characterized by tonic response to sound is a heterogeneous one in the functional respect. An assumption that some neurons of the tonic type are inhibitory interneurons of the auditory cortex, other excitatory ones is under discussion.     

Auditory response properties and spatial response areas of single neurons in the pontine nuclei of the big brown bat, Eptesicus fuscus.

Using free-field acoustic stimulation conditions, we studied the response properties and spatial sensitivity of 146 pontine neurons of the big brown bat, Eptesicus fuscus. The best frequency (BF) and minimum threshold (MT) of a pontine neuron were first determined with a sound broadcast from a loudspeaker placed ahead of the bat. A BF sound was delivered from the loudspeaker as it moved across the frontal auditory space in order to locate the response center at which the neuron had its lowest MT. Then the basic response properties of the neuron to a sound delivered from the response center were studied. As in inferior collicular and auditory cortical neurons, pontine neurons can be characterized as phasic responders, phasic bursters and tonic responders. They have both monotonic and non-monotonic intensity-rate functions. However, most of them are broadly tuned as are cerebellar neurons. Auditory spatial sensitivity was studied for 144 pontine neurons. In 9 neurons, variation of MT with a BF sound delivered from several azimuthal and elevational angles along the horizontal and vertical planes crossing the neuron's response center was measured. In addition, variation in the number of impulses with several stimulus intensities at 10 dB increments above a neuron's MT delivered from each angle was also studied. The auditory spatial sensitivity of other pontine neurons was studied by measuring the response area of each neuron with stimulus intensities at 3, 5, 10, 15 or 40 dB above its lowest MT. The response areas of pontine neurons expanded asymmetrically with stimulus intensity, but the size of the response area was not correlated with either MT or BF. In half of the pontine neurons studied, the response area expanded greatly and eventually covered almost the entire frontal auditory space. The response areas of the other half of the pontine neurons only expanded to a restricted area of frontal auditory space. Two possible neural mechanisms underlying these two types of response areas are hypothesized. The response centers of all 144 neurons were located within a small area of the frontal auditory space. The locations of response centers of these neurons are not correlated with their BFs. The distribution pattern of these response centers is comparable to that of superior collicular and cerebellar neurons but is different from that of inferior collicular and auditory cortical neurons. The results of our study suggest that auditory information is integrated in the pontine nuclei before being further sent into the cerebellum.     

Regulation of slow potential shifts in nucleus reticularis thalami by the mesencephalic reticular formation and the frontal granular cortex.

Novel stimuli or electric stimulation of the mesencephalic reticular formation (MRF) produced large positive slow potentials (SPs) in rostral nucleus reticularis thalami (RVA) that accompanied the negative SPs known to occur in frontal cortex. SP durations (20-30 sec) were similar to the periods of unit inhibition that occur in RVA following MRF stimulation. Trains of 8 c/sec medial thalamic stimuli produced phasic negative SPs in RVA similar in duration to the intervals of unit excitation that follow each stimulus pulse. These results suggest that the polarity and duration of the SPs in RVA reflect changes in excitation of the underlying neurons. Direct activation of a specific region of RVA produced complete inhibition of visual cortex responses evoked by optic tract stimuli, a finding which suggests that RVA has an inhibitory action on the thalamus. A tone reinforced by electric shock also elicited SPs in frontal cortex (negative) and RVA (positive). In contrast to the long duration of the MRF- or novelty-elicited SPs, the durations of the conditioned SPs were phasic and were regulated by the tone--shock interval. Bilateral cryogenic blockade of the interconnections between the frontal cortex and medial thalamus abolished SPs of all origins in the frontal cortex. The blockade also abolished conditioned SPs in RVA, but did not affect the MRF-elicited ones. Thus, the subcortical SPs that accompany orienting to novel stimuli are distinct from those which occur during the higher cognitive process of conditioned expectancy and require the integrity of the mediothalamic-frontocortical system.     

Neuronal Sianallina of Information Imoortant to Visual Recognition-Memory in Rat Rhinal aid Neighbouring Cortices

This study was conducted to discover whether the rat cortex contains neurons that signal information concerning the previous occurrence of stimuli, as has been found in the primate. Recordings of the activity of 396 single neurons were made while unanaesthetized rats were shown objects. The effects on neuronal responsiveness of stimulus repetition and of the relative familiarity of the stimuli were sought. The areas sampled were the rhinal (entorhinal and perirhinal) cortex, area TE of the temporal cortex, the lateral occipital cortex and the hippocampal formation. The response to the first presentations of objects was significantly different from that to their second presentations for 63 (34%) of the 185 responsive neurons; for 39 of the neurons the response was smaller when the stimulus was repeated, whereas for 24 it was larger. The incidence of decremental responses was higher in the non-hippocampal cortex than in the hippocampal formation, while the incidence of incremental responses was higher in the hippocampal formation than other cortical areas. The response to unfamiliar objects was significantly different from that to highly familiar objects for 15 (22%) of 67 responsive neurons so tested; for 12 of the neurons the response was smaller when the stimulus was repeated, and for three it was larger; most of these neurons were found in area TE. The responses of ten familiarity neurons varied significantly with the relative familiarity of the stimuli but not with stimulus repetition; the responses of seven recency neurons varied significantly upon stimulus repetition but not with the relative familiarity of the stimuli. Thus information concerning stimulus repetition and familiarity is separably encoded at the single neuron level in the rat cortex. The results demonstrate that in the rat cortex as in the monkey cortex there are neurons that signal information concerning the prior occurrence of stimuli; such information is of importance to recognition memory, working memory and priming memory.     

Tolerances of responses to visual patterns in neurons of the posterior inferotemporal cortex in the macaque against changing stimulus size and orientation, and deleting patterns

Neuronal activities were recorded in areas TEO and TE of the inferotemporal cortex in four hemispheres of two monkeys during the performance of a visual pattern discrimination task. Tolerances of responses to patterns against changing stimulus size and orientation, and deleting patterns halves were investigated and compared between TEO and TE neurons. Of 311 neurons tested, 80 (26%) responded to one or more patterns out of four standard patterns. Of these 80 neurons, 50 (63%) were recorded in area TEO and 30 (38%) in area TE. Neurons responsive to patterns were recorded in both areas TEO and TE, however degrees of tolerance of responses were different between TEO and TE neurons. Tolerances of TEO neurons were moderate and degrees of tolerance varied from neuron to neuron. Responses to particular patterns were dependent on stimulus size, stimulus orientation, and/or completeness of patterns. By contrast, tolerances of TE neurons were generally strong. Responses to particular patterns were not affected by changing stimulus size, changing stimulus orientation nor deleting patterns halves. These results suggest that area TEO rather than area TE is involved in detecting and processing particular visual shapes.     

Auditory spatial response areas of single neurons and space representation in the cerebellum of echo locating bats

Using free-field acoustic stimulation conditions, we studied the auditory spatial response areas of 242 cerebellar neurons of Eptesicus fuscus. A best frequency stimulus was delivered from a loudspeaker which was moved across the frontal auditory space in order to determine the response center of each cerebellar neuron. At the response center, the neuron had its lowest minimum threshold. The stimulus was then raised 5-15 dB above the lowest minimum threshold of each neuron and the spatial response area for each stimulus intensity was measured. The spatial response area of each neuron expanded asymmetrically with the stimulus intensity. The size of the spatial response area was not correlated with the minimum threshold, best frequency or recording depth of the neuron. The distribution of the best frequencies of single neurons was not correlated with their recording depths or minimum thresholds. The response centers of all cerebellar neurons were located within a small area of the central portion of the frontal auditory space suggesting that the cerebellum could play an effective role in orienting the bat toward the echo source within the frontal gaze during insect capture.