Kindling phenomenon of hyperthermic seizures in the epilepsy-prone versus the epilepsy-resistant rat

A kindling-like effect was produced by exposing 30-day-old rats to repeated hyperthermia-induced seizures. Naive audiogenic seizure (AGS)-susceptible rats (P77PMC) were easier to be kindled than AGS-resistant rats (Wistar). This hyperthermic kindling model may be used to study the outcome and mechanisms of human febrile seizures. The mechanisms underlying hyperthermic kindling remain to be investigated.     

Seizure activity in the rat hippocampus,perirhinal and prefrontal cortex associated with transient global cerebral ischemia

Summary. Epileptiform EEG activity associated with ischemia can contribute to early damage of hippocampal neurons, and seizure activity may also lead to dysfunction in extrahippocampal regions. In this study, seizure activity associated with the four-vessel occlusion model of cerebral ischemia was monitored using chronically implanted electrodes in the CA1/subicular region, the perirhinal cortex, and the prefrontal cortex of the rat. Background EEG amplitude was reduced in all recording sites during occlusion, but spiking and bursting activity was also observed. Seizure activity occurred in most animals during the first several hours of reperfusion, but was not observed on subsequent days. Epileptiform spikes and bursts were often synchronous between two or three recording sites, and spikes in the CA1 region also often occurred just prior to spikes in other sites. These results demonstrate that the four-vessel occlusion model can lead to patterns of seizure activity in the hippocampus, prefrontal and perirhinal cortices. Correspondence: C. Andrew Chapman, Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, 7141 Sherbrooke Street West, Rm. SP-244, Montreal, Quebec, H4B 1R6 Canada     

The rat claustrum: Afferent and efferent connections with visual cortex

We have examined the afferent and efferent projections between the claustrum and visual cortex in the Long-Evans rat using anterograde and retrograde axonal transport techniques. Injections of either wheat germ agglutinin/horseradish peroxidase (WGA/HRP) or Fast Blue were made into each of the main visual regions (17, 18a or 18b) as well as directly into the claustrum. The cortical injections were placed in either the upper, middle or deep layers so as to assist in determining the laminar organization of these connections. Of the 3 visual areas, only area 18b appears to have extensive and reciprocal connections with the claustrum. After a WGA/HRP injection of this area, dense labeled terminals and numerous labeled cells were found intermixed throughout the full extent of the claustrum. The density of this labeled activity was found to vary directly with the amount of the infragranular layers involved by the injections. Injections in the other visual areas did produce labeled cells in the claustrum, but their number was always small or even negligible. There was never any evidence of anterograde labeled terminals in the claustrum from any injection of areas 17 or 18a. Tracer injections directly in the claustrum confirmed and extended these findings by showing that the labeled terminals and/or labeled cells were localized predominantly in layer VI of area 18b of visual cortex. On the basis of these injections, two major conclusions are reached. First, the pattern of connections between the claustrum and visual cortex in the rat differs fundamentally with that found in other species.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rostral agranular insular cortex and pain areas of the central nervous system: a tract-tracing study in the rat

The rostral agranular insular cortex (RAIC) has recently been identified as a site where local changes in GABA and dopamine levels, or application of opioids, can alter nociceptive thresholds in awake animals. The connections of the cortex dorsal to the rhinal fissure that includes the RAIC have been examined previously, with emphasis on visceral and gustatory functions but not nociception. Here we examined the afferent and efferent connections of the RAIC with sites implicated in nociceptive processing. Sensory information from the thalamus reaches the RAIC via the submedius and central lateral nuclei and the parvicellular part of the ventral posterior nucleus. The RAIC has extensive reciprocal cortico-cortical connections with the orbital, infralimbic, and anterior cingulate cortices and with the contralateral RAIC. The amygdala, particularly the basal complex, and the nucleus accumbens are important targets of RAIC efferent fibers. Other connections include projections to lateral hypothalamus, dorsal raphe, periaqueductal gray matter, pericerulear region, rostroventral medulla, and parabrachial nuclei. The connectivity of the RAIC suggests it is involved in multiple aspects of pain behavior. Projections to the RAIC from medial thalamic nuclei are associated with motivational/affective components of pain. RAIC projections to mesolimbic/mesocortical ventral forebrain circuits are likely to participate in the sensorimotor integration of nociceptive processing, while its brainstem projections are most likely to contribute to descending pain inhibitory control.     

Differential BDNF signaling in dentate gyrus and perirhinal cortex during consolidation of recognition memory in the rat

Consolidation of long‐term memory is dependent on synthesis of new proteins in the hippocampus and associated cortical regions. The neurotrophin brain‐derived neurotrophic factor (BDNF) is tightly regulated by activity‐dependent cellular processes and is strongly linked with mechanisms underlying learning and memory. BDNF activation of tyrosine receptor kinase (TrkB) stimulates intracellular signaling cascades implicated in plasticity, including the extracellular‐signal related kinase (ERK)/mitogen‐activated protein kinase (MAPK) pathway and the phosphatidylinositide‐3‐kinase (PI3K)/Akt pathway. Here, we investigate the role of BDNF, ERK/MAPK, and PI3K/AKT signaling cascade in recognition memory in the rat. We report that recognition memory was associated with increased release of BDNF in the dentate gyrus and perirhinal cortex. This was associated with significant increases in p44ERK activation and c‐fos expression in the dentate gyrus and PI3K activation and c‐fos expression in the perirhinal cortex. Furthermore, both recognition memory and the associated cell signaling events in dentate gyrus and perirhinal cortex were blocked by intraperitoneal injection of the Trk receptor inhibitor tyrphostin AG879. These data are consistent with the hypothesis that BDNF‐stimulated intracellular signaling plays a role in consolidation of recognition memory in the rat. © 2012 Wiley Periodicals, Inc.     

Temporary inactivation of the perirhinal cortex by muscimol injections block acquisition and expression of fear-potentiated startle

The present study examined the role of the perirhinal cortex (PRh) in aversive information processing and emotional learning. Specifically, we studied the effects of temporary inactivation of the PRh on acquisition and expression of conditioned fear as measured by fear-potentiated startle in rats, as well as on shock sensitization of startle. Temporary inactivation of the PRh was induced by local injections of the GABAA agonist muscimol (0.0, 1.1, 2.2, 4.4 nmol/0.5 micro L). Muscimol injections into the PRh blocked both the expression and acquisition of fear-potentiated startle, as well as shock sensitization of startle. Shock sensitivity was not affected by muscimol injections, indicating that the observed blockade of acquisition and shock sensitization was not caused by a disruption in the perception of shock. Taken together, the present data show that the PRh is critical for the processing of aversive information and is necessary for the expression of emotional learning.     

A direct projection from the perirhinal cortex (area 35) to the subiculum in the rat

An efferent projection from the perirhinal cortex (area 35) in the rat was studied using the anterograde transport of triated amino acids as well as horseradish peroxidase (HRP). Following injections of either tracer in either the dorsal or ventral parts of area 35, anterogradely transported label was observed in the molecular layer of the subiculum, adjacent prosubiculum and CAla. Regardless of the dorsoventral level of the injection, the label was most dense at mid-dorsoventral levels of the subiculum and decreased in density in both the septal and temporal directions. Small injections of the same tracers made into the surrounding entorhinal, ectorhinal or prepiriform cortices did not reproduce this pattern. While the entorhinal cortex is the main cortical source of afferent input to the molecular layer of the subiculum as well as the hippocampus and dentate gyrus, the perirhinal cortex appears to constitute a complementary cortical pathway for afferent input to the subiculum.     

Epileptiform synchronization in the rat insular and perirhinal cortices in vitro

The hippocampus plays a primary role in temporal lobe epilepsy, a common form of partial epilepsy in adults. Recent studies, however, indicate that extrahippocampal areas such as the perirhinal and insular cortices represent important participants in this epileptic disorder. By employing field potential recordings in the in vitro 4-aminopyridine model of temporal lobe epilepsy, we have investigated here the contribution of glutamatergic and GABAergic signaling to epileptiform activity in these structures. First, we provide evidence of epileptiform synchronicity between the perirhinal and insular cortices, and resolve some pharmacological and network mechanisms involved in sustaining the interictal- and ictal-like discharges recorded there. Second, we report that in the absence of ionotropic glutamatergic transmission, GABAergic networks produce synchronous potentials that spread between the perirhinal and insular cortices. Finally, we have established that such activity is modulated by activating µ-opioid receptors. Our findings support clinical and experimental evidence concerning the involvement of the perirhinal and insular cortex networks in temporal lobe epilepsy, and provide observations that may impact research focussing on the role of the insular cortex in nociception.     

Neurophysiology of limbic system pathways in the rat: Projections from the amygdala to the entorhinal cortex

We studied the responses of rat entorhinal neurons to electrical stimulation of the amygdala. Four main results were obtained: (1) excitatory postsynaptic potentials were recorded in entorhinal neurons in response to electrical stimulation of the amygdala. Cells in layers II, III and V of the entorhinal cortex were responsive. (2) Excitatory responses were followed by inhibitory postsynaptic potentials. (3) Frequency potentiation of both excitatory and inhibitory responses was observed when 10/s stimulation was used. (4) Three amygdala neurons were antidromically activated by entorhinal stimulation; and two layer II entorhinal cells that were excited by amygdala stimulation were also antidromically activated by dentate gyrus stimulation. These results provide evidence for a monosynaptic, excitatory projection from the amygdala to the entorhinal cortex. In addition, the data indicate that amygdala neurons are only one synapse removed from the excitation of dentate gyrus granule cells.     

Projections from the amygdaloid complex to the claustrum and the endopiriform nucleus: a Phaseolus vulgaris leucoagglutinin study in the rat

The claustrum and the endopiriform nucleus contribute to the spread of epileptiform activity from the amygdala to other brain areas. Data of the distribution of pathways underlying the information flow between these regions are, however, incomplete and controversial. To investigate the projections from the amygdala to the claustrum and the endopiriform nucleus, we injected the anterograde tracer Phaseolus vulgaris leucoagglutinin into various divisions of the amygdaloid complex, including the lateral, basal, accessory basal, central, anterior cortical and posterior cortical nuclei, the periamygdaloid cortex, and the amygdalohippocampal area in the rat. Analysis of immunohistochemically processed sections reveal that the heaviest projections to the claustrum originate in the magnocellular division of the basal nucleus. The projection is moderate in density and mainly terminates in the dorsal aspect of the anterior part of the claustrum. Light projections from the parvicellular and intermediate divisions of the basal nucleus terminate in the same region, whereas light projections from the accessory basal nucleus and the lateral division of the amygdalohippocampal area innervate the caudal part of the claustrum. The most substantial projections from the amygdala to the endopiriform nucleus originate in the lateral division of the amygdalohippocampal area. These projections terminate in the central and caudal parts of the endopiriform nucleus. Lighter projections originate in the anterior and posterior cortical nuclei, the periamygdaloid cortex, the medial division of the amygdalohippocampal area, and the accessory basal nucleus. These data provide an anatomic basis for recent functional studies demonstrating that the claustrum and the endopiriform nucleus are strategically located to synchronize and spread epileptiform activity from the amygdala to the other brain regions. These topographically organized pathways also provide a route by means of which the claustrum and the endopiriform nucleus have access to inputs from the amygdaloid networks that process emotionally significant information.     

Kindling of the Visual Cortex in Cats: Comparison with Amygdaloid Kindling

Abstract: Kindling of the primary visual cortex (VC) was compared with that of the amygdala in cats. VC kindling was basically similar to kindling of the amygdala in that daily electrical stimulation can lead to the development of a generalized convulsion in most subjects, a growth of afterdischarges in their configuration and duration, and a reduction of the afterdischarge threshold. The kindling response of the VC differed from that of the amygdala in a number of respects, i.e., a high afterdischarge threshold, a different pattern of behavioral seizure development, an abrupt growth of electroclinical seizures coincident with the onset of a generalized convulsion, an intersubject variability in seizure susceptibility, and a marked seizure instability. In VC kindling the afterdischarge propagation into the amygdala was not observed until the generalized convulsion developed, and the early involvement of afterdischarge was seen in the pulvinar, lateral geniculate body, and superior colliculus. These data suggest that a neural mechanism different from amygdaloid kindling may participate in VC kindling, and that the sub-cortical structures of the visual system are involved in the preferential pathway for a seizure generalization from the VC.     

Sleep quality and its association with the insular cortex in emotional empathy

The human ability to vicariously share someone else's emotions (i.e., emotional empathy) relies on an extended neural network including regions in the anterior cingulate and insular cortex. Here, we tested the hypothesis that good sleep quality is associated with increased activation in the brain areas underlying emotional empathy. To this aim, we assessed subjective sleep quality in a large sample of healthy young volunteers, and asked participants to complete a computerized emotional empathy task. Then, we asked 16 participants to complete the same task while undergoing functional Magnetic Resonance Imaging (fMRI). After confirming the behavioral relationship between quality of sleep and emotional empathy in the large sample, we conducted a Region of Interest (ROI) analysis on selected ROIs involved in emotional empathy, and measured Blood Oxygen Level Dependent (BOLD) signal change in participants who performed the emotional empathy task in the MRI scanner; additionally, we assessed how the BOLD signal in different brain areas temporally correlated with performance throughout the task (i.e., task‐based functional connectivity). We found increased BOLD signal change in a selective region within the left insula for individuals with better subjective sleep quality. These findings provide the very first evidence that individuals’ sleep quality relates to emotional empathic responses through increased neural activation of a specific area within the insular cortex.     

Propagation of Epileptiform Activity During Development of Amygdala Kindling in Rats: Linear and Non-linear Association Between lpsi- and Contralateral Sites

The relationship between ipsi- and contralateral epileptiform electroencephalographic (EEG) activity was investigated in rats that were kindled daily in the amygdala. Two types of relationship—linear and non-linear associations—were studied and used to estimate time delays of EEG activity between homotopic amygdalar sites during consecutive tetanizations. The progressive development of epileptiform EEG and convulsive behaviour was accompanied by an increase in association. Maximal association values of the non-linear function were significantly higher than linear association values. The gradual development of motor seizure severity was correlated with increased non-linearity. Time delays between the two amygdalae were estimated comparably with the linear and non-linear function: 30.0±3.3 and 24.6±1.7 ms (ipsilateral leading contralateral), respectively. However, in rats displaying exclusively bilaterally generalized motor convulsions, maximal values of both functions decreased but were still significantly higher than control values of phaserandomized EEG. Corresponding positive as well as negative interhemispheric time delays were recorded during the afterdischarge. These results demonstrated a strengthened association between the ipsi-and contralateral amygdala during primary epileptogenesis induced by amygdala kindling. In contrast, development of a secondary focus in the contralateral homotopic region resulted in a weakened interhemispheric association. Secondary bilateral synchrony between the ipsi- and contralateral amygdala occurred during the evoked epileptiform EEG activity.     

Physiological evidence for an excitatory pathway from entorhinal cortex to amygdala in the rat

We studied the responses of amygdala neurons to entorhinal cortex stimulation in anaesthetized rats. Intracellular and extracellular data were obtained in a total of 16 cells located throughout the amygdaloid complex and two cells in adjacent piriform cortex. In addition, antidromic responses to amygdala stimulation were obtained in 7 cells of the entorhinal or perirhinal cortex. All recordings in the amygdala showed orthodromic excitatory responses (spikes or EPSPs), with a mean latency of 8 ms. These were succeeded by IPSPs with a mean latency of 15 ms. Two cells in piriform cortex responded to entorhinal stimulation with inhibition alone. A cell in the region of the basomedial nucleus showed characteristics of an inhibitory interneuron. Cells in entorhinal and perirhinal cortex responding antidromically to amygdala stimulation were found primarily in layers III-V. Axons of one such cell, which was injected with HRP, were seen to course rostrally to the region of the amygdala within the fiber tract of the external capsule. Three entorhinal cells (layer III) responded antidromically to both amygdala and hippocampal formation stimulation. A neuronal circuit diagram accounting for our findings is presented.     

Afferent connections of the perirhinal cortex in the rat

Connections of the perirhinal cortex in the.rat brain were studied using anterograde (³H-proline/leucine) and retrograde (horseradish peroxidase) tracers. The perirhinal cortex receives major projections from medial precen-tral, anterior cingulate, prelimbic, ventral lateral orbital, ventral and posterior agranular insular, temporal, superior and granular parietal, lateral occipital, agranular retrosplenial, and ectorhinal cortices, and from the pre-subiculum, subiculum, and diagonal band of Broca. Rostral neocortical areas project predominantly to rostral perirhinal regions while more caudal neocortical and subicular areas project predominantly to caudal perirhinal regions. Terminal fields are further segregated within perirhinal cortex to either the dorsal or ventral banks of the rhinal sulcus. All afferents from frontal areas terminate predominantly in the deep layers of its ventral bank; afferents from temporal, parietal, and lateral occipital areas terminate predominantly in the deep and superficial layers along its dorsal bank; and afferents from ectorhinal cortex terminate in a column within its dorsal bank. Cortical cells which project to perirhinal areas are found predominantly in layer II and the superficial part of layer III. However, ventrolateral orbital, parietal, and lateral occipital cortex projections originate predominantly from layer V. Perirhinal areas also receive afferents from the nucleus reuniens of the thalamus, lateral nucleus of the amygdala, claustrum, supramammillary nuclei, and the dorsal raphe nuclei.     

Effects of insular cortex lesions on conditioned taste aversion and latent inhibition in the rat

The present study tested the hypothesis that lesions of the insular cortex of the rat retard the acquisition of conditioned taste aversions (CTAs) because of an impairment in the detection of the novelty of taste stimuli. Demonstrating the expected latent inhibition effect, nonlesioned control subjects acquired CTAs more rapidly when the conditioned stimulus (0.15% sodium saccharin) was novel rather than familiar (achieved by pre-exposure to the to-be-conditioned taste cue). However, rats with insular cortex lesions acquired taste aversions at the same slow rate regardless of whether the saccharin was novel or familiar. The pattern of behavioural deficits obtained cannot be interpreted as disruptions of taste detection or stimulus intensity, but is consistent with the view that insular cortex lesions disrupt taste neophobia, a dysfunction that consequently retards CTA acquisition because of a latent inhibition-like effect.     

Relation of the insular claustrum to the neocortex in Insectivora.

The claustra of 9 species of Insectivora (Sorex araneus, Sorex minutus, Tenrec ecaudatus, Solenodon paradoxus, Neomys fodiens, Erinaceus europaeus, Talpa europaea, Desmana moschata, Potamogale velox) were investigated. In all examined animals we found two parts of the insular claustrum: the main part called by us the pars principalis and more medially situated lamina profunda claustri. In the "basal" Insectivora the main part is in close contact with the layer VIa of the neocortex. In some more developed "basal" and in all "progressive" Insectivora the area capsularis appears. Dorsolaterally it separates the main part of the insular claustrum from the neocortex and possesses, besides neurons, also numerous fibers of the extreme capsule. The above data strongly suggest that in the phylogenesis the insular claustrum originates from the cortex from which it gets separated by the extreme capsule. Lamina profunda claustri is rather a narrow band of neurons situated on the medial side of the pars principalis and mostly separated from it by a thin lamina of white substance. Lamina profunda is continuous with the layer VIb of the neocortex.     

Neuropeptide changes following excitotoxic lesion of the insular cortex in rats

Following middle cerebral artery occlusion in Wistar rats, the immunoreactivity of neuropeptide Y increased ipsilaterally in the insular cortex and basolateral nucleus of the amygdala. In addition, the immunoreactivity of leucine-enkephalin, dynorphin, and neurotensin increased in the ipsilateral central nucleus of the amygdala. The amygdalar neurochemical changes are likely the result of damage to the insular cortex, although other cortical areas were also affected by the ischemia. To investigate whether damage to the insular cortex is essential in eliciting these changes, a localized lesion of the right or left insular cortex was produced by microinjection of D,L-homocysteic acid. Control animals received injections of vehicle into the right or left insular cortex or D,L-homocysteic acid into the right primary somatosensory cortex. Neurochemical changes were examined immunohistochemically with the peroxidase antiperoxidase reaction 5 lays after the injection. The immunoreactivity of neuropeptide Y increased locally after excitotoxic damage to the insular cortex or primary somatosenaory cortex. The amygdalar neurochemical changes, including neuropeptide Y increase in the basolateral nucleus and leucine-enkephalin, dynorphin, and neurotensin increase in the central nucleus, were seen only when the ipsilateral insular cortex was lesioned. These neurochemical changes were similar to those seen 5 days after middle cerebral artery occlusion. Our findings indicat that damage to the insular cortex is essential in eliciting the neurochemical changes in the ipsilateral amygdala. In addition, the change in neuropeptide Y in the cortex appears to be a local reaction occurring irrespective of location of the lesion and glutamate receptor activation may be involved. © 1995 Wiley-Liss Inc.     

Kindling in the deep prepyriform cortex of the rat

Rats were electrically kindled in deep prepyriform cortex (DPC) and in immediately surrounding areas, pyriform cortex, and the basolateral amygdala in an effort to identify an area of the basal forebrain crucially involved in epileptogenesis and the kindling of seizures. Picomolar quantities of carbachol were also microinjected into DPC. All of these areas kindled at equivalent rates. Injection of picomolar quantities of carbachol failed to evoke epileptiform spiking, but injection of nanomolar quantities of carbachol usually evoked epileptiform spiking. Bilateral radiofrequency lesions of the DPC did not affect the rate of electrical kindling of the basolateral amygdala. We conclude that the DPC kindles readily at a rate that is similar to that of surrounding basal forebrain tissue and that the integrity of the DPC is not necessary for basolateral amygdaloid kindling.