Prepyriform Research Articles

Cerebral transplants for seizures: preliminary results.

Several critical brain regions have been identified in which application of gamma-aminobutyric acid (GABA) potentiating agents in small quantities can suppress or prevent generalized and kindled amygdala seizures, i.e., substantia nigra and deep prepiriform cortex. Severity of audiogenic seizures in the genetically epilepsy prone rat (GEPR) is reduced by injection of norepinephrine (NE) into the lateral ventricles and by GABA in inferior colliculus. The present investigation examines the potential for raising epileptic thresholds by increasing local GABAergic or NE inhibitory activity by means of brain transplants of tissue rich in GABA or NE neurons. Two models of epilepsy were used: amygdala-kindled seizures and sound-induced seizures in GEPRs. Transplantation of embryonic cerebellar or cortical tissue to the deep prepiriform area of amygdala kindled rats transiently raised seizure thresholds in three of the nine animals. Transplantation of embryonic cerebellar or cortical tissue to the inferior colliculus or adrenal medulla tissue to lateral ventricles of GEPRs did not appreciably reduce the intensity of audiogenic seizures in these animals.

Neuroanatomical regions of the chick brain involved in monitoring amino acid deficient diets

Chicks fed a diet deficient in tryptophan will reduce food intake dramatically. Chicks will select a balanced diet over one that is deficient in tryptophan (trp). The amygdala and prepiriform cortex have been implicated in monitoring amino acid (AA) balanceand hence food intake in rats. Therefore, comparable regions of the chick brain were studied to determine if they were involved in monitoring AA deficient diets. In each of four experiments, 48 chicks were used (24 experimentally-operated and 24 sham-operated controls). After starting on a commercial diet, chicks were fed semipurified diets: balanced (bal) or trp deficient (def). The following dietary regimen was followed in all experiments in both pre- and postoperatively; 1. 1) bal diet for an adjustment period; 2. 2) bal diet for 1–2 days; 3. 3) def diet for 2–3 days; 4. 4) choice of both diets presented simultaneously. This was followed by ablation of a brain region and then a repetition of the dietary regimen. Brain regions ablated or isolated include the nucleus taeniae (Tn), piriform cortex (CPi), frontal archistriatum (FA) and ventral archistriatum (AV). No differences in selection were observed when lesions ablating the FA, AV or Tn were performed. A significant decrease in selection of the bal diet was observed after knife cuts which isolated the piriform cortex from medial connections. It is suggested that this brain region may be involved in monitoring AA profiles in the plasma.

Gamma-Vinyl GABA in endopiriform area suppresses kindled amygdala seizures.

Suppression of kindled amygdala seizures in rats followed bilateral infusion of the GABA transaminase inhibitor gamma-vinyl-GABA (GVG) into the endopiriform area of the forebrain. The deep prepiriform cortex of the rat is an important site for both initiation and arrest of generalized seizures induced by systemic convulsants. To determine whether this area also regulates the spread of amygdala seizures, the irreversible GABA-transaminase blocking agent, GVG (vigabatrin) was infused bilaterally in the deep prepiriform area in amygdala-kindled rats. Twenty-four hours after the infusion, kindled seizure threshold was elevated in 12 of 13 rats tested. If homologous areas exist in the primate brain, treatment strategies that take advantage of critical areas for seizure spread by local infusion of inhibitory agents or transplantation of GABA-containing cells may be developed for suppressing intractable seizures in humans.

Deep prepiriform cortex lesion and development of amygdala kindling.

The effects of a unilateral thermocoagulating lesion of the deep prepiriform cortex on the development of amygdala kindling were studied in adult rats. The lesion did not alter the local excitability of the ipsilateral amygdala. Furthermore, the number of stimulations required to produce generalized seizures did not significantly differ between lesioned and control animals. The results suggest that the deep prepiriform cortex may not be important in the development of amygdala kindling.

Inhibition of the development of electrical kindling of the prepyriform cortex by daily focal injections of excitatory amino acid antagonists

The effects of daily focal injections of excitatory amino acid antagonists into the prepyriform cortex on the development of electrically kindled seizures at this site were studied. The selective ‘NMDA receptor’ antagonists 2-amino-7-phosphonoheptanoic acid (AP7) and 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CCP) significantly inhibited the development of the electrically evoked afterdischarge over a 10 day period and prevented the development of the motor seizure responses. The ‘kainate and quisqualate receptor’ antagonist γ-D-glutamylaminomethyl sulphonic acid (GAMS) showed less potent but still significant inhibitory actions on these responses. When drug treatment ceased, kindling progressed in all animals at a rate similar to that of the control (buffer-treated) animals. These results suggest a critical role for NMDA receptors in the primary neuronal events initiating the epileptiform activity in this animal model of epilepsy.

Organization of cortical and subcortical projections to medial prefrontal cortex in the cat

We have analyzed the cortical and subcortical afferent connections of the medial prefrontal cortex (MPF) in the cat with the specific aim of characterizing subregional variations of afferent connectivity. Thirteen tracer deposits were placed at restricted loci within a cortical district extending from the proreal to the subgenual gyrus. The distribution throughout the forebrain of retrogradely labeled neurons was then analyzed. Within the thalamus, retrogradely labeled neurons were most numerous in the mediodorsal nucleus and in the ventral complex. The projection from each region exhibited continuous topography such that more medial thalamic neurons were labeled by tracer from more ventral and posterior cortical deposits. Marked retrograde labeling without any sign of topographic order occurred in a narrow medioventral sector of the lateroposterior nucleus. Several additional thalamic nuclei contained small numbers of labeled neurons. In a subset of nuclei closely affiliated with the limbic system (the parataenial, paraventricular, reuniens, and basal ventromedial nuclei), retrograde labeling occurred exclusively after deposits at extremely ventral and posterior cortical sites. Within the amygdala, retrogradely labeled neurons occupied the anterior basomedial nucleus, the posterior basolateral nucleus, and a narrow strip of the lateral nucleus immediately adjoining the basolateral nucleus. The number of labeled neurons was greater after more ventral deposits. Very ventral deposits resulted in extensive labeling of the cortical amygdala. Within the cerebral cortex, the distribution of labeled neurons depended on the location of the tracer deposit. Comparatively dorsal deposits produced prominent retrograde transport to the anterior and posterior cingulate areas, to the agranular insula, and to lateral prefrontal cortex. Comparatively ventral deposits gave rise to prominent labeling of the hippocampal subiculum, various parahippocampal areas, and prepiriform cortex. On the basis of afferent connections, it is possible to divide the cat's medial prefrontal cortex into an infralimbic component, MPFil, marked by strong afferents from prepiriform cortex and the cortical amygdala, and a dorsal component, MPFd, without afferents from these structures. Further, within MPFd, it is possible to define an axis, running from ventral and posterior to dorsal and anterior levels, along which limbic afferents gradually become weaker and projections from cortical association areas gradually become stronger.

Differential distribution of β and θ EEG activity in the entorhinal cortex of the cat

The basic characteristics of the electroencephalograms (EEGs) of the entorhinal cortex (EC) were compared to those of the olfactory bulb (OB) and prepiriform cortex (PPC) in the awake cat, using methods that take into account linear (coherence functions) and non-linear relationships (mutual information). The frequency spectra of EC signals recorded from OB or PPC, but in the β frequency band (35–40Hz) coherent activity between these latter two areas and the EC could be put in evidence. Taking the values of coherence as a measure of linear coupling between populations of neurons, this coupling is strong between PPC and the rostral part of the EC, and becomes weaker towards more lateral, caudal and medial areas. This decrease in coupling is confirmed by non-linear analysis methods. On the basis of intracortical dep in layer II of the EC. Another rhythmic activity was also recorded in EC in the θ frequency range. Theta rhythm is generated mainly in the caudal part of EC. This area has the strongest coupling with the hippocampal formation. These analyses lead to the conclusion that in the EC olfactory and limbic domains have different topographical distributions but with a certain degree of overlap.

Adenosine receptor activation blocks seizures induced by bicuculline methiodide in the rat prepiriform cortex

Adenosine receptor activation blocks seizures induced by bicuculline methiodide in the rat prepiriform cortex

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.

Excitant amino acids and audiogenic seizures in the genetically epilepsy-prone rat. II. Efferent seizure propagating pathway

Previous studies indicate that the inferior colliculus is the brain stem auditory nucleus most sensitive to the chemical blockade of audiogenic seizures in the genetically epilepsy-prone rat. Other auditory structures do not appear to be as important. This study attempted to define the efferent pathways involved in propagation of the seizure from the colliculus to the spinal cord where the motor components of the convulsion are generated. This study also determined whether certain nuclei which have been implicated in the propagation of seizures in other epilepsy models are involved in audiogenic seizures. The excitant amino acid antagonist, 2-amino-7-phosphonoheptanoate, was infused bilaterally into several of those sites. The drug was effective in significantly reducing seizure severity with infusion of 5 nmol bilaterally into the midbrain and the pontine reticular formation or the substantia nigra. However, similar drug doses were not effective when infused into the entopeduncular nucleus even though prominent behavioral effects were observed with this infusion. Infusion of 2-amino-7-phosphonoheptanoate into the prepiriform cortex resulted in a small but significant reduction in seizure severity. These results suggest that inhibition of excitatory transmission within the substantia nigra and the reticular formation effectively blocks the output pathway for the audiogenic seizures, whereas the role of the prepiriform cortex in this process is relatively minor.

Reciprocal connections of the insular and piriform claustrum with limbic cortex: An anatomical study in the cat

The connections of the claustrum with non-isocortical limbic and paralimbic cortex in the cat are described, using the anterograde transport of tritiated amino acids and the retrograde transport of various fluorescent tracers and of horseradish peroxidase conjugated to the lectin wheatgerm agglutinin. It could be demonstrated that the claustrum, in addition to its connections with sensory-related areas, is reciprocally and bilaterally connected with widespread limbic and paralimbic cortical regions. These connections are organized such that the area of origin of claustral efferents to a certain cortical region coincides with the area of termination in the claustrum of afferents from that same cortical region. A rostrocaudal topographical organization of the limbic-related connections of the claustrum is not very apparent. However, the results clearly demonstrate a dorsoventral topographical organization in the connections between the claustrum and the cortex. The ventral part of the claustrum has reciprocal connections predominantly with the entorhinal cortex and possibly with the anterior olfactory nucleus and the prepiriform cortex. A more dorsally located part of the claustrum is preferentially connected with the orbitofrontal, the insular, the perirhinal, the anterior limbic and the cingular cortices and with parts of the subicular complex. The most dorsal portion of the claustrum is more heavily connected with parasensory and sensory cortices. It is concluded that the traditional subdivision of the claustrum into two discrete nuclei, i.e. the insular claustrum connected with the isocortex and the piriform claustrum or endopiriform nucleus connected with the allocortex, does not reflect the actual organization of the cortical connections of the claustrum. The present data provide a more differentiated view, such that the ventral portion of the claustrum is reciprocally connected mainly with the olfactory-related cortices and the entorhinal cortex, whereas the cortical connections of progressively more dorsal parts of the claustrum gradually shift from limbic and paralimbic towards parasensory and sensory cortical connections. The significance of these findings is discussed in the light of a possible function of the claustrum in relation to corticocortical integration and memory processing.

Organization of the afferent connections of the mediodorsal thalamic nucleus in the rat, related to the mediodorsal-prefrontal topography

The aim of the present study was to determine the organization of the afferents of the mediodorsal thalamic nucleus in relation to the reciprocal connections of this nucleus with different areas of the prefrontal cortex. For this purpose injections of horseradish peroxidase, or horseradish peroxidase conjugated to wheatgerm agglutinin were placed in different parts of the mediodorsal nucleus. These experiments revealed the organization of the reciprocal mediodorsal-prefrontal connections since wheatgerm agglutinin-horseradish peroxidase is transported effectively in anterograde and retrograde directions. Injections of wheatgerm agglutinin-horseradish peroxidase or fluorescent tracers were placed in different portions of the prefrontal cortex, and the lectin Phaseolus vulgaris leucoagglutinin was injected in the mediodorsal nucleus in order to verify in more detail the point-to-point relationship in the mediodorsal-prefrontal connections. The organization of a number of the subcortical afferents to the mediodorsal nucleus was determined in detail using injections of Phaseolus vulgaris leucoagglutinin, wheatgerm agglutinin-horseradish peroxidase, or tritiated amino acids in areas identified as a source of mediodorsal afferents in the retrograde tracing experiments. These anterograde tracers were injected in different parts of the pallidal complex, the amygdala, the lateral hypothalamus, the lateral entorhinal cortex, the ventral mesencephalon, the superior colliculus and the dorsal tegmental region. The results of the present experiments indicate that the mediodorsal nucleus, on the basis of its cyto-, myelo- and chemoarchitecture as well as the organization of its reciprocal connections with the prefrontal cortex, can be subdivided into a medial, a central, a lateral and a paralamellar segment. Apart from this subdivision along a mediolateral axis, rostrocaudal and dorsoventral differences are also evident in the structural organization and connectivity of the mediodorsal nucleus. A number of subcortical structures send fibres to all parts of the mediodorsal nucleus. The reticular thalamic nucleus projects to the mediodorsal nucleus in a topographical way such that its rostral part is connected with the rostral part of the nucleus, whereas more caudal and ventral areas in the reticular thalamic nucleus are connected with more caudal parts of the mediodorsal nucleus. Regions in the brainstem that project to all parts of the mediodorsal nucleus include the mesencephalic raphé nuclei, the locus coeruleus, the rostral part of the central gray substance and the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

The involvement of excitatory amino acid receptors within the prepiriform cortex in pilocarpine-induced limbic seizures in rats.

The prepiriform cortex (PPCx) shows high sensitivity to the epileptogenic action of chemo-convulsants and to the protective action of the NMDA receptor antagonist, 2-amino-7-phosphono-heptanoate (APH) against pilocarpine-induced (motor) limbic seizures in rats. In this study the interaction between agonists acting selectively on the three main excitatory amino acid receptor subtypes in the PPCx and the muscarinic agonist, pilocarpine, within the PPCx have been investigated. Kainate (KA) or quisqualate (QUIS) injected focally into the PPCx (100 pmoles or 5 nmoles per side respectively) induced motor limbic seizures when administered after a subconvulsant dose of pilocarpine (250 mg/kg, i.p.). KA, 100 pmoles injected into the same site in olfactory-bulboectomized rats (bulbectomy results in protection against pilocarpine-induced seizures) also facilitated seizures. However, activation of the NMDA receptor in the PPCx by focal injection of NMDA (250 fmoles-10 nmoles) failed to produce seizures after a subconvulsant dose of pilocarpine. Moreover NMDA in the same range of doses injected into the PPCx protected rats against the seizures induced by a fully convulsant dose of pilocarpine.

Effects of corticosterone on shaking and seizure behavior induced by deep prepyriform cortex kindling.

The influence of adrenocorticosteroids on seizures and wet dog shakes (WDS) induced by deep prepyriform cortex kindling was studied by bilateral adrenalectomy and corticosterone replacement. The rate of kindling, latency to the onset and duration of motor seizures were not significantly affected by adrenalectomy or corticosterone treatment. However, the number of WDS observed after stage 5 seizures was reduced in adrenalectomized animals and it was not restored until 3 h following corticosterone replacement. This delay in onset of action suggests that the effects of adrenocorticosteroids and/or ACTH on WDS may be mediated by an indirect mechanism.

Immunocytochemical localization of cholecystokinin and glutamic acid decarboxylase during normal development in the prepyriform cortex of rats

Immunocytochemical localization of specific neurotransmitters in the brain is becoming increasingly important in studies of maturation. We have used the trilaminar prepyriform cortex (PC) of rats to study the distribution, patterns and relative number of cells, fibers and terminals during postnatal development using antisera to cholecystokinin (CCK) and glutamic acid decarboxylase (GAD). Both antisera show distinct patterns of immunoreactivity at birth and subsequent periods of distinct changes in these patterns. CCK immunoreactivity is rare but present at birth mostly in layer II. There is a dramatic increase of CCK-labeled structures between postnatal (PN) days 6 and 9 and between PN 13 and 21. The adult pattern is observed by PN 21 with large numbers of labeled cells in layer II, numerous terminals in layers II and deep I and large immunoreactive fibers in the lateral olfactory tract. At birth GAD-immunoreactive terminals are present mainly in layer I, forming a distinct pattern of superficial and deep bands. Subsequent major changes occur in this pattern between PN 9 and 13 and again between PN 13 and 21. By PN 21 there appears to be a loss in deeper laminae of GAD positive terminals which are possibly replaced by the increasing numbers of CCK terminals in the same sublaminae. The adult pattern of GAD immunoreactivity is established by PN 21 with terminals and a few cells in layer I. Therefore, throughout development of the rat PC, there is a distinct complementary and changing distribution of GAD and CCK. Factors that may influence these changes in immunoreactivity are discussed.

The Prepiriform Cortex in Dementia of the Alzheimer Type

Histopathologic examination of the prepiriform cortex (PPC) in four documented cases of dementia of the Alzheimer type revealed increased numbers of neurofibrillary tangles and neuritic plaques. These findings indicate that some early- and late-onset cases of Alzheimer's disease may be associated with significant damage to the PPC, a relay center of the mammalian olfactory system that has extensive connections with structures concerned with cognitive and behavioral functions. Involvement of the PPC may be related to the complex neuropsychiatric manifestations observed in this disorder.

Simulation of chaotic EEG patterns with a dynamic model of the olfactory system.

The main parts of the central olfactory system are the bulb (OB), anterior nucleus (AON), and prepyriform cortex (PC). Each part consists of a mass of excitatory or inhibitory neurons that is modelled in its noninteractive state by a 2nd order ordinary differential equation (ODE) having a static nonlinearity. The model is called a KOe or a KOi set respectively; it is evaluated in the "open loop" state under deep anesthesia. Interactions in waking states are represented by coupled KO sets, respectively KIe (mutual excitation) and KIi (mutual inhibition). The coupled KIe and KIi sets form a KII set, which suffices to represent the dynamics of the OB, AON, and PC separately. The coupling of these three structures by both excitatory and inhibitory feedback loops forms a KIII set. The solutions to this high-dimensional system of ODEs suffice to simulate the chaotic patterns of the EEG, including the normal low-level background activity, the high-level relatively coherent "bursts" of oscillation that accompany reception of input to the bulb, and a degenerate state of an epileptic seizure determined by a toroidal chaotic attractor. An example is given of the Ruelle-Takens-Newhouse route to chaos in the olfactory system. Due to the simplicity and generality of the elements of the model and their interconnections, the model can serve as the starting point for other neural systems that generate deterministic chaotic activity.

Deep prepiriform cortex kindling and amygdala interactions

The deep prepiriform cortex (DPC) has been recently suggested to be a crucial epileptogenic site in the rat brain. We investigated the susceptibility of the DPC to the development of electrical kindling as compared to that of the superficial prepiriform cortex (SPC) and amygdala as well as the transfer interactions between the two prepiriform sites and amygdala. Adult rats with electrodes implanted in the right prepiriform cortex (DPC or SPC) and left amygdala were divided into a DPC-amygdaia and SPC-amygdala group while a third group consisted of rats with electrodes implanted in the ipsilateral DPC and amygdala. Within each group the rats were initially kindled from one site selected randomly and then rekindled from the other site. Both DPC and SPC were as sensitive to the development of kindling as the amygdala. The behavioral seizures elicited with DPC or SPC primary kindling were identical to those induced by amygdala kindling. Initial DPC kindling facilitated the development of kindling from either ipsilateral or contralateral amygdala with the ipsilateral transfer being significantly more potent than the contralateral. SPC kindling also facilitated the development of contralateral amygdala kindling but was less effective than DPC kindling. On the other hand, amygdala kindling did not facilitate contralateral SPC or DPC kindling although it transferred to the ipsilateral DPC. These results indicate that the prepiriform cortex can be readily kindled but not faster than the amygdala and that there are unequal kindling transfer interactions between prepiriform cortex and amygdala.

Anticonvulsant effects of GABA elevation in the deep prepiriform cortex

Microinjection of gamma-vinyl GABA (GVG), a GABA elevating agent, into a discrete region of the deep prepiriform cortex elevated local GABA levels nearly 4-fold and exerted an anticonvulsant action against seizures induced by intravenous injection of the GABA antagonist, bicuculline, but was ineffective against seizures induced by maximal electroshock. This, together with a previous finding that blockade of GABA transmission in the deep prepiriform cortex induces convulsions, suggests that this area may be crucial, if not primarily responsible, for the genesis of clonic seizures resulting from a deficit in GABA function.

The deafferented reticular thalamic nucleus generates spindle rhythmicity.

The hypothesis that nucleus reticularis thalami (RE) is the generator of spindle rhythmicity during electroencephalogram (EEG) synchronization was tested in acutely prepared cats. Unit discharges and focal waves were extracellularly recorded in the rostral pole of RE nucleus, which was completely disconnected by transections from all other thalamic nuclei. In some experiments, additional transections through corona radiata created a triangular island in which the rostral RE pole survived with the caudate nucleus, putamen, basal forebrain nuclei, prepyriform area, and the adjacent cortex. Similar results were obtained in two types of experiments: brain stem-transected preparations that exhibited spontaneous spindle sequences, and animals under ketamine anesthesia in which transient spindling was repeatedly precipitated during recording by very low doses of a short-acting barbiturate. Both spindle-related rhythms (7- to 16-Hz waves grouped in sequences that recur with a rhythm of 0.1-0.3 Hz) are seen in focal recordings of the deafferented RE nucleus. The presence of spindling rhythmicity in the disconnected RE nucleus contrasts with total absence of spindles in cortical EEG leads and in thalamic recordings behind the transection. Oscillations within the same frequency range as that of spontaneous spindles can be evoked in the deafferented RE nucleus by subcortical white matter stimulation. In deafferented RE cells, the burst structure consists of an initially biphasic acceleration-deceleration pattern, eventually leading to a long-lasting tonic tail. Quantitative group data show that the burst parameters of disconnected RE cells are very similar to those of RE neurons with intact connections. In the deafferented RE nucleus, spike bursts of RE neurons recur periodically (0.1-0.3 Hz) in close time-relation with simultaneously recorded focal spindle sequences. The burst occurrence of deafferented RE cells is greatly reduced after systemic administration of bicuculline. The preservation of both spindle-related rhythms in the disconnected RE nucleus, together with our recent experiments showing abolition of spindle oscillations in thalamic nuclei after lesions of RE nucleus (24), demonstrate that RE nucleus is the generator of spindle rhythms.