Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded. The response to a conditioning stimulus was compared to the response to a test stimulus delivered 500 ms later: the ratio of the test response to the conditioning response provided a measure of inhibitory gating. Auditory-evoked potentials were recorded at all sites. Overall, brainstem reticular nucleus neurons showed the greatest gating of local auditory-evoked potentials, while the auditory cortex showed the least. However, except for the auditory cortex, both gating and non-gating of the evoked response were recorded at various times in all brain regions. Gating of the hippocampal response was significantly correlated with gating in the medial septal nucleus and brainstem reticular nucleus, but not the auditory cortex. Single-unit neuron firing in response to the clicks was most pronounced in the brainstem reticular nucleus and the medial septal nucleus, while relatively few neurons responded in the CA3 region of the hippocampus and the auditory cortex. Taken together, these data support the hypothesis that inhibitory gating of the auditory-evoked response originates in the non-lemniscal pathway and not in cortical areas of the rat brain.     

Cat P300 present after primary auditory cortex ablation

A long-latency (200-500 msec) endogenous potential with characteristics of the human P300 was recorded over 12 sessions in 4 adult cats. Principal components analysis with t tests showed that this potential was significantly larger in response to rare auditory stimuli than to the same stimuli presented frequently. The primary auditory cortex was ablated bilaterally. The preoperative tone-elicited conditioned eye blink response remained postoperatively. After 12 postoperative sessions, statistical analyses of these data demonstrated that the P300-like potential was still present. Thus, the primary auditory cortex is not necessary for generation of the P300-like response in cats.     

'Cat P300' disappears after septal lesions

Endogenous responses were recorded from 9 awake cats with loud and soft clicks randomly presented as rare (P = 0.15) or frequent (P = 0.80) stimuli; a reinforced tone CS (P = 0.05) resulted in a conditioned eye blink response and focused the cat's attention on the auditory stimuli. Subsequent to 12 preoperative recording sessions the medial septal area was lesioned in 7 cats and similar but more rostral lesions were placed in 2 cats. Thereafter, 12 postoperative recording sessions were carried out, the animals were terminated, and the brains processed for AChE histochemistry and histology of the lesioned areas. Destruction of the medial septum and vertical limb of the diagonal band of Broca resulted in a transient postoperative 'cat P300' followed by reduction and disappearance of the response. The hippocampus of these animals was characterized by marked AChE depletion. In contrast, the animals with lesions rostral to the medial septal area showed no postoperative change in the P300 response and no depletion of hippocampal AChE. These data indicate an important role for the medial septal area as a modulator of 'cat P300' generation possibly through the cholinergic component of the septohippocampal projection system.     

The effect of peripheral stimulation on the electrical activity of the neocortex in chronic premesencephalic cats]

Chronic experiments were carried out with 19 adult cats. It is demonstrated that following a premesencephalic sectioning of the brain stem, with the lemniscal pathways being spared, on the second and third day after the surgery, auditory, olfactory and skin stimulations caused diffusive activation of the neocortex. Photic stimulation, though evoking responses in the visual cortex, was unable to desynchronize the neocortical electrical activity. Taking into account the data on the organization of hypothalamic afferent connections, it is suggested that diffuse activation of the neocortex in cats, when the mesencephalic reticular formation is completely excluded, occurs during auditory, olfactory and skin stimulations due to excitation of the posterior hypothalamus.     

Influence of chloralose on brain regional glucose utilization

Choralose, a widely used anesthetic in neurophysiology, produces a unique pattern of anesthesia characterized by both an excitant (myoclonic jerks and startle response) and depressant (sedation and anesthesia) action. We investigated the influence of chloralose on the rate of regional brain glucose metabolism to determine if chloralose produces anesthesia by hyperexciting certain brain regions. That is, does chloralose act as an ‘epileptoid anesthetic’. Rats were anesthetized with either 60 or 120 mg/kg chloralose and regional brain glucose utilization rates quantitated by the 2-deoxyglucose method. In chloralose-anesthesized rats, glucose consumption rates decreased in the frontal and auditory cortex, reticular nucleus of thalamus, superior colliculus, medial geniculate body, midbrain reticular formation and hippocampus. Rates of glucose use were not decreased in the lateral lemniscus and a zone in the vicinity of the oculomotor nucleus, medial longitudinal fasciculus and surrounding reticular formation. Since chloralose did not induce any discernible focal points of high activity, chloralose appears not to be an epileptogen. Rather, chloralose appears to act as a general depressant except in certain gray areas of the midbrain and lower brain stem. Retained and possibly increased functional activity in the vicinity of the oculomotor nucleus and medial longitudinal fasciculus may represent active reflex pathways involved in mediating the paradoxical startle response and myoclonic activity observed in chloralose-anesthetized animals.     

Spike-wave rhythms in cat cortex induced by parenteral penicillin. I. Electroencephalographic features.

Surface and depth recordings were made in 21 cats with generalized, parenteral penicillin induced epileptiform activity often assuming spike-wave forms, to obtain information on the structural substrate of "spontaneous" spike-wave rhythms. Recordings were made from neocortex, medial and lateral thalamus, hippocampus and brainstem reticular formation. Epileptiform activity first appeared in cortex and subsequently projected to depth structures. Occasionally, focal discharges could be seen in subcortical structures, but these generally did not spread to cortex. No consistent "pacemaker" was identified in cortex or depth. Bilateral applications of penicillin to cortex produced synchronous spike-wave bursts. In contrast, ventriculocisternal perfusion of penicillin solutions yielded synchronous cortical potentials which differed clearly in morphology and frequency from parenterally induced spike-wave bursts. During generalized activity, transcortical, intrahemispheric lesions interfered with ipsilateral synchrony. After transcortical section, projection of localized cortical bursts to thalamus did not necessarily result in "recruitment" of diffuse cortical regions into epileptiform activity. These results emphasize the importance of cortical circuitry and corticocortical connections in the genesis and synchronization of spike-wave rhythms.     

Acoustic responses and plasticity of limbic units in cats

Multiple-unit and single-unit responses to monaurally applied acoustic stimuli were recorded from hippocampal, amygdalar, reticular, and auditory pathway nuclei in awake. paralyzed cats. A range of motivationally neutral, 1-sec pure tones or white noise evoked markedly different response forms (excitation or inhibition) or magnitudes within the hippocampus and amygdala as a function of both the laterality of stimulus presentation and the quality (frequency) of the acoustic stimulus. The responses typically had relatively long latencies, and the response durations often outlasted the stimulus periods for several hundred milliseconds. During repetitive stimulation with either pure tones or white noise, responses at recording sites in all regions exhibited magnitude decrements (habituation), dishabituation, and spontaneous recovery, These response changes usually, but not always, occurred in parallel at limbic, reticular, and auditory pathway sites. Some degree of specific information about the environment is thus available to the hippocampus and amygdala, where stimulus effects may be modified by experience. The characteristics of the the units recorded in this study are contrasted to those in previous reports of selectively and persistently responsive limbic units in freely moving subjects presented with motivationally significant stimuli. The functional organization of the hippocampus and amygdala in sensory processing and their relation to reticular and auditory systems is discussed.     

Midlatency auditory evoked responses: differential effects of sleep in the cat

Middle latency responses (MLRs) in the 10-100 msec latency range, evoked by click stimuli, were studied in 8 adult cats during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. In particular, we wanted to determine whether the 20-22 msec positivity recorded at the vertex, 'wave A,' shown in previous studies to reflect a generator substrate within the ascending reticular formation, was tightly linked to changes in sleep-wakefulness, as reported for single neurons in the ascending reticular activating system. Evoked potentials were collected in 100 trial averages during continuous presentation of 1/sec clicks during initial awake recordings and thereafter during all-night sleep sessions. Continuously recorded EEG, EOG and EMG were scored for wakefulness, slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. Recordings were obtained from electrodes implanted at the vertex and overlying the primary auditory cortex referenced to frontal sinus or to neck. In agreement with others, components of the auditory brain-stem response and the 12 msec primary cortical response showed no change in amplitude from wakefulness to either SWS or REM. Only wave A, among the components evaluated in the 1-100 msec range, decreased and disappeared during SWS and dramatically reappeared during REM to an amplitude equal to that during wakefulness. These data lend particular support to a functional relation between wave A and the ascending reticular activating system and suggest that this potential may provide a unique and dynamic probe of tonic brain activity. Moreover, this animal model provides a hypothetical basis for expecting a similar surface recorded potential in the human, a potential which has consequently been discovered.     

Habituation of the orienting response elicited by stimulation of the caudate nucleus in the cat

High frequency (100/sec) electrical stimulation of eight points in the head of the caudate nucleus in six unanesthetized, freely moving cats yielded an orienting response from all points. The behavior observed was indistinguishable from the orienting response elicited by novel, acoustic stimulation and by electrical stimulation of the amygdala, parts of cortex, and the mesencephalic reticular formation.

The cats habituated to the caudate stimulation just as cats habituate to non-signal, peripheral sensory events. The same has previously been found for stimulation of amygdala and cortex, while no habituation is observed to stimulation of the mesencephalic reticular formation.     

Transient global ischemia specifically modulates visual P300 scalp distribution.

OBJECTIVE: Latency, amplitude, and scalp topography of the visual P300 component was examined in patients who had suffered from transient global ischemia (TGI) due to cardiac arrest and in age matched clinical and healthy controls in order to investigate the diagnostic value of this component. METHOD: Event-related potentials (ERPs) were recorded from 19 scalp electrodes in a visual oddball paradigm. RESULTS: Mean latency of the P300 component was prolonged in both patient groups. Changes in scalp distribution of the P300, however, appear to be specific to anoxic-ischemic encephalopathy. In particular, a selective reduction of the P300 amplitudes at posterior recording sites was observed in TGI patients. Moreover, examination of the auditory P300 in TGI patients revealed that this selective change seems to be restricted to the visual modality. CONCLUSION: The results are discussed with respect to selective vulnerability of brain tissue to hypoxic-ischemic injury. After TGI a modality-specific subset of P300 generators, probably located in the transitional parieto-occipital and extrastriate occipital cortex, appears to be affected. It is also noted, that the visual P300 component could serve as an additional marker of TGI especially in patients who do not show neuropathological changes in structural brain images.     

An application of long-term frequency analysis in measuring drug-specific alterations in the EEG of the cat.

A method is described for the quantitative measurement of "drug-specific" effects on the EEG of the cat. These effects are dose-related and are independent of the normal sources of EEG variation associated with the sleep-waking cycle. Drug-induced changes are expressed as characteristic alterations in frequency spectra and the time courses of these effects are followed for 5 h following administration of the test compounds. Atropine sulfate (0.5 and 2.0 mg/kg) and physostigmine salicylate (0.05 and 0.20 mg/kg) were administered to three unanesthetized and unrestrained cats and a broad-band frequency analysis was performed on the spontaneous brain electrical activity recorded from the prepyriform cortex, ventral hippocampus, lateral geniculate nucleus and the midbrain reticular formation. The resulting data were used as input to discriminant and canonical statistical analysis programs employed to abstract "drug-specific" patterns of frequency change. It was found that both atropine and physostigmine produce alterations in EEG frequency spectra which are clearly distinct from those patterns associated with the sleep-waking cycle and thus neither compound results in what has been characterized as an "EEG-behavioral dissociation".     

Electrophysiological study of the central and peripheral hearing system of aphasic individuals

SUBJECT: Electrophysiology of the auditory system. OBJECTIVE: Electrophysiological evaluation of the peripheral and central auditory system of brain injured patients. METHOD: Experimental group: eleven brain injured and aphasic subjects, both genders and with ages ranging from 43 to 75; control group: eleven individuals without hearing complaints, equalized as to gender and age. The subjects were evaluated through auditory brainstem response (ABR); auditory middle latency response (AMLR) and auditory P300 response. RESULTS: An increase in the V wave latency and I-V interpeak in both groups, due to the age factor. The presence of statistically significant hemispheric differences when compared to the Pa component in MLAEP research, registered in the C3 (left hemisphere) and the C4 (right hemisphere). In researching the P300 Cognitive Potential, there was an absence or increase in P300 latency and a decrease in P300 amplitude in the presence of the N2 component. CONCLUSION: The AMLR and auditory P300 response have proven to be effective instruments for evaluating aphasic individuals.     

Task-relevant late positive component in rats: Is it related to hippocampal theta rhythm?

Long-latency components of event-related potentials (like the P300 or P3) correlate with the ability of subjects to detect and process unexpected, novel or task-relevant events. Task-relevant late positive components were recorded in the neocortex and hippocampus of rats performing an auditory discrimination task, similar to the “odd-ball” paradigm used in human experiments. Surface and depth electrodes were implanted in anaesthetized rats at frontal, temporal and anterior occipital neocortical regions and the hippocampus. After recovery from surgery rats were trained to discriminate two auditory signals, a frequent irrelevant tone and a rare tone related to water reward. In response to the task-relevant tone but not the irrelevant tone, P300-like late positive components (mean latency of 274 ms) were recorded throughout the surface of the neocortex. The largest amplitudes were found at the anterior occipital cortex situated above the hippocampal CA1 region. The amplitude of the task-relevant positive component increased further with cortical depth without reversing its polarity. An amplitude maximum was found in the CA1 region with a polarity reversal at the pyramidal cell layer and the largest negative amplitude in stratum radiatum. Power spectra of differences between responses evoked by task-relevant tones and those evoked by irrelevant tones revealed peaks in the theta range (4–12 Hz). It is suggested that the P300-like component in rats corresponds to a theta wave out of a burst of hippocampal theta cycles. © 1996 Wiley-Liss, Inc.     

Magnetic resonance imaging in schizophrenia: altered brain morphology associated with P300 abnormalities and eye tracking dysfunction.

This study was designed to investigate whether auditory P300 event-related potential and smooth pursuit eye-movement abnormalities in schizophrenia are associated with brain structural changes measured using magnetic resonance imaging (MRI). Serial coronal MRI scans obtained from 31 schizophrenic subjects and 33 volunteer controls were analysed by a rater who had no knowledge of the subjects' diagnoses. The brain areas measured bilaterally were the temporal lobe, hippocampus, amygdala, parahippocampal gyrus, head of caudate, cingulate cortex, frontal cortex, and the lateral ventricles. The area of the third ventricle, the thickness of the corpus callosum, and the intracranial area were also measured. Auditory P300 and eye tracking performance were recorded on all subjects. There was a significant increase in the latency and a reduction in amplitude of the P300 in the schizophrenic group. Only in the schizophrenic group was P300 latency correlated negatively with the area of the right and left cingulate cortex and positively with the difference in size between the right and left amygdala. In the subgroup of schizophrenic subjects whose P300 latency was greater than 2 standard deviations above the control mean, the area of the left cingulate cortex was significantly smaller than in controls, and the absolute right-left difference in the area of the amygdala was significantly increased. Eye tracking dysfunction in schizophrenia was not related to changes in the amygdala or cingulate cortex but was significantly correlated with enlargement of the lateral ventricles. Schizophrenic subjects with poor eye tracking had significantly larger lateral ventricles than controls. Eye tracking dysfunction, but not P300 abnormality, was correlated with the severity of both positive and negative symptom of schizophrenia. These findings demonstrate that psychophysiological abnormalities are associated with altered brain structure in schizophrenia.     

Findings and reflections on the reverberation of thalamocortical impulses]

Chang's experiments showing the rhythmic afterdischarge in slightly nembutalized cats which he considered as a manifestation of the activity of thalamocortical reverberating circuits, prompted us to study the origin of the afterdischarge in the auditory cortex arising in response to single sound clicks on unanesthetized immobilized and nembutalized cats. The rhythmic afterdischarge was found to be most pronounced at light anesthesia with a tendency of background activity to synchronization, which may be evidenced by rare bursts of spindles. During the prolonged spontaneous desynchronization as well as during stimulation of mesencephalic reticular formation no rhythmic afterdischarge and no spontaneous bursts of spindles arose. With a deepening of anesthesia slow afterdischarge undergoes precisely the same changes as spontaneous spindle bursts (the duration tends to increase for a while with a subsequent decrease, the frequency and then the amplitude of waves decrease and eventually they disappear altogether). These and other findings suggest that rhythmic afterdischarge of the auditory cortex arising to sound clicks seems to be similar to the evoked spindle in response to peripheral and central stimulations. It was reported in many previous and recent papers. The fact, that following the cooling or ablation of the auditory cortex the rhythmic afterdischarge to sound clicks as well as spontaneous spindle bursts keep arising in the medial geniculate body without changing their patterns, militates also against the possibility of thalamocortical reverberation.     

Effects of bemegride on the sensory responses of neurons in the hippocampus and brain stem reticular formation

Administration of subconvulsant doses of bemegride results in extensive enhancement of sensory responsiveness to auditory, visual, somatosensory and vibrissa stimulation of neurons in the medullary and mesencephalic reticular formation (RF). This effect is not altered by cord transection. Most neurons in the dorsal hippocampus do not show enhanced sensory responsiveness. In the minority of hippocampal neurons which do show enhancement the effect is much less extensive than that seen in the RF despite larger doses of bemegride. The enhancement of RF neuronal response may involve the reversal of repetition induced response attenuation ('habituation') and reductions in response threshold. During EEG seizures the firing of neurons in RF and hippocampus are temporally correlated with the spikes in the cortical EEG. The effects of bemegride on RF neurons are similar to those previously reported for strychnine and pentylenetetrazol and preliminary studies with physostigmine and bicuculline. These findings further extend the concept that a relatively selective enhancement of the sensory responses of brain stem reticular formation neurons may be indicative of a general neuronal effect of convulsants which may play an important role in the initiation of sensory-induced seizures.     

Mesencephalic and bulbar reticular formation influences on somatosensory transmission through the thalamus

The influence of the brain stem reticular formation (RF) on transfer of somatosensory information has been studied in intact cats and in cats with a chronic hemisection of the brain stem at the pretrigeminal level. An air-jet applied to the hairy skin receptive field evoked the discharge of thalamocortical relay cells in nucleus ventralis postero-lateralis, extracellularly recorded. Conditioning stimuli were brief trains of electrical pulses to mesencephalic (MRF) and bulbar (BRF) reticular formation. In intact cats both MRF and BRF induced in a small percentage of cells slight facilitation or inhibition of evoked discharge. In pretrigeminal cats MRF stimulation increased the probability of discharge in response to peripheral stimuli, whereas BRF stimulation induced a striking decrease in evoked firing in a great percentage of neurones. It is suggested that RF activation can decrease the incoming peripheral volley by means of its caudalmost part, while it is able to enhance thalamic response by way of the more rostral structures.     

Midlatency auditory-evoked responses: effect of scopolamine in the cat and implications for brain stem cholinergic mechanisms

The objective of this study has been to define the role of cholinergic mechanisms in the generation of "wave A," a middle latency auditory-evoked potential recorded as a positivity with a 20-25 ms peak latency from the vertex of conscious cats. Wave A and its generator system have particular significance as an experimental model of the human middle latency component "P1." Both the feline wave A and the human P1 are characterized by a long recovery cycle, disappearance during slow wave sleep, and reappearance during rapid eye movement (REM) sleep and during wakefulness. The orchestration of several phenomena of REM sleep are known to involve muscarinic cholinergic mechanisms in the brain stem. Therefore, middle latency auditory-evoked potentials were studied in awake cats before and after injection of a cholinergic antagonist, scopolamine. Wave A and the successive negative potential were abolished by scopolamine in a dose-dependent fashion. This effect occurred within 5-15 min and was spontaneously reversible within a few hours. Although individual subjects were differentially susceptible to lower doses of the drug, all six subjects in this study demonstrated a well-defined statistically significant response at higher doses of the drug. In addition, careful parametric baseline studies were performed in each cat to strengthen the evidentiary linkage between wave A as recorded from the vertex in these experiments and previous studies describing the origin and trajectory of wave A in the brainstem reticular formation and several regions of thalamus, including the intralaminar nuclei. Thus, we conclude that the production of wave A depends substantially on the postsynaptic activation of muscarinic cholinergic receptors whose cells of origin lie within the brainstem reticular formation.     

Barbiturate-induced glycogen accumulation in brain. An electron microscopic study

Glycogen accumulation in the mouse brain during prolonged barbiturate anesthesia (6 h with sodium phenobarbital, 250 mg/kg) was studied with the electron microscope. Areas examined included hypothalamus, hippocampus (area dentata), midbrain reticular formation, cerebellar cortex and frontal cerebral cortex. Large increases of particulate glycogen were noted in astrocytes of the area dentata and the frontal cortex. Smaller increases were sometimes seen in astrocytes of the cerebellar cortex. No changes were noted in the hypothalamus or midbrain reticular formation and glycogen was never seen in neurons, oligodendroglia or microglia. The greatest accumulation of astrocytic glycogen occured in areas of high synaptic density and near neuronal perikarya.     

A compound P300-40 Hz response of the cat hippocampus.

In companion reports (Ba?ar-Eroglu et al., in press a,b) it was shown that the hippocampal P300 response had a frequency content with prominent theta enhancement, especially near CA3 region. Moreover, frequency analysis revealed a marked component in the 40 Hz frequency range. In the present study, a detailed account about "40 Hz response accompanied by the N200-P300 compound response" is given. These results were obtained by use of digital adaptive filtering method described in previous studies (Ba?ar et al., 1987, Ba?ar, 1980). The physiological interpretation of the visual 40 Hz component gained tremendous importance since the discovery of Gray and Singer (1987, 1989) of 40 Hz oscillations in the visual cortex. Our analysis shows clearly that the 40 Hz response component is not only a cortical response pattern. Moreover, the 40 Hz response is accompanied by a P300 response and we discuss that it is also a universal building block of brain responsiveness. The 40 Hz response should be correlated with multimodal sensory and cognitive function.