Chronic amphetamine treatment affects collicular-dependent behaviour.

Distractibility can be defined as an attention deficit where orientation toward irrelevant targets cannot be inhibited. There is now mounting evidence that the superior colliculus is a key neural correlate of distractibility, with increased collicular-activity resulting in heightened distractibility. Heightened distractibility is reduced by amphetamine, which acutely suppresses collicular responsiveness. However, when amphetamine is used to treat distractibility, it is given chronically, yet no data exist on whether chronic amphetamine treatment affects the colliculus. Here, the effect of chronic amphetamine treatment was assessed in healthy hooded lister rats on two collicular dependent behaviours following a twenty-eight day treatment period: i) orienting to visual stimuli, and ii) height-dependent modulation of air-righting. We found no significant impact of amphetamine treatment on visual orienting despite showing dose-dependent decreases in orienting to repeated stimuli. However, we did find that treatment with amphetamine significantly reduced the ability to modulate righting according to the height the animal is dropped from - a function known to be dependent on the colliculus. We suggest that the results are in line with previous research showing acute amphetamine suppresses collicular activity and we speculate that the psychostimulant may increase receptive field size, altering time-to-impact calculations carried out by the colliculus during air-righting.

[Effect of reboxetine on activity of carboxypeptidase E in the nerve tissue of rats].

Depression is one of the most common mental disorders, but its etiology is not completely understood. It is assumed that peptidergic system components are involved in the formation of this pathology. Neuropeptides play an important role in the regulation of mental and emotional states. Сarboxypeptidase E is a key enzyme of peptide processing; it regulates neuropeptide levels in the various structures of the nervous system. We have studied effects of a single dose of reboxetine on the activity of carboxypeptidase E in various brain regions and the adrenal glands of rats. The reboxetine injection decreased carboxypeptidase E activity in the pituitary gland (12 h after injection), in the pituitary gland, the quadrigeminal bodies, the medulla oblongata, the hypothalamus, the hippocampus and the amygdala (24 h after injection), in the pituitary gland and striatum (72 h after injection). The enzyme activity in adrenal glands remained basically unchanged. Apparently, the decrease of carboxypeptidase E activity may influence the level of regulatory peptides involved in the pathogenesis of depression.

Nicotinic potentiation of frog retinotectal transmission in tectum layer F by α3ß2, α4ß2, α2ß4, α6ß2, or α7 acetylcholine receptor subtypes.

OBJECTIVE: The aim of the study was to explore the effect of semi-specific antagonists and agonists of the nicotinic acetylcholine receptors on the paired-pulse facilitation and nicotinic tonic and phasic potentiation of the frog retinotectal synaptic transmission. MATERIALS AND METHODS: The experiments were performed in vivo on adult frogs, Rana temporaria. An individual retina ganglion cell (or its retinotectal fiber) was stimulated by current pulses delivered through multichannel stimulating electrode positioned on the retina. Responses to a discharge of a single retinal ganglion cell were recorded in the tectum by an extracellular carbon-fiber microelectrode positioned in the terminal arborization of the retinotectal fiber in the tectum layer F. The effect of the antagonists and agonists of the nicotinic acetylcholine receptors on the tectal responses has been tested. RESULTS: We found that the antagonists, MLA and DHßE, and agonists, RJR-2403 and choline, of the nicotinic acetylcholine receptors of the α3ß2, α4ß2, α2ß4, α6ß2 or α7 subtypes have had no effect on the phasic and tonic potentiation of the retinotectal transmission. The paired-pulse facilitation of the retinotectal transmission was not appreciably affected by the antagonists, but the choline, agonist of the α7 subtype receptor, has significantly decreased the paired-pulse facilitation. CONCLUSIONS: The tonic and phasic potentiation of the retinotectal transmission in the tectum layer F were not mediated by the receptors of α3ß2, α4ß2, α2ß4, α6ß2 or α7 subtype. The results suggest that presynaptic nicotinic acetylcholine receptors of the frog optic fibers are different from those of the mammalian optic fibers.

Intraocular BDNF promotes ectopic branching, alters motility and stimulates abnormal collaterals in regenerating optic fibers.

A great deal of effort has been invested in using trophic factors and other bioactive molecules to promote cell survival and axonal regeneration in the adult central nervous system. Far less attention has been paid to investigating potential effects that trophic factors may have that might interfere with recovery. In the visual system, BDNF has been previously reported to prevent regeneration. To test if BDNF is inherently incompatible with regeneration, BDNF was given intraocularly during optic nerve regeneration in the adult goldfish. In vivo imaging and anatomical analysis of selectively labeled axons were used as a sensitive assay for effects on regeneration within the tectum. BDNF had no detectable inhibitory effect on the ability of axons to regenerate. Normal numbers of axons regenerated into the tectum, exhibited dynamic growth and retractions similar to controls, and were able to navigate to their correct target zone in the tectum. However, BDNF was found to have additional effects that adversely affected the quality of regeneration. It promoted premature branching at ectopic locations, diminished the growth rate of axons through the tectum, and resulted in the formation of ectopic collaterals. Thus, although BDNF has robust effects on axonal behavior, it is, nevertheless, compatible with axonal regeneration, axon navigation and the formation of terminal arbors.

Recruitment of striatonigral disinhibitory and nigrotectal inhibitory GABAergic pathways during the organization of defensive behavior by mice in a dangerous environment with the venomous snake Bothrops alternatus (Reptilia, Viperidae).

The neuropsychopharmacological basis of fear- or panic-related behavior has been the focus of several studies. Some mesencephalic tectum (MT) structures, such as the superior colliculus (SC) and dorsal periaqueductal gray matter (dPAG), are considered to be responsible for the control of defensive responses evoked during threatening situations. Furthermore, the pars reticulata of the substantia nigra (SNpr) sends inputs to the SC that can work as a sensory channel to MT neurons fundamental for the elaboration of defensive responses. The purpose of the present study was to investigate the role of striato-nigral GABAergic inputs in the activity of nigro-tectal outputs during the elaboration of defensive behavior using a GABA(A) receptor selective blockade in the MT of mice confronted pre-treated with Bothrops alternatus. Mice with injections of physiological saline into the SNpr and treated with a GABA(A) receptor selective antagonist in the MT displayed an increase in panic-related behavior, expressed by an increase in the duration of freezing, frequency of nonoriented escape and frequency of total escape responses during the confrontation with the snake. However, intra-SNpr injections of cobalt chloride followed by MT injections of bicuculline caused a significant decrease in the duration of freezing and total escape responses. In addition, intra-SNpr injections of lidocaine followed by MT injections of bicuculline caused an increase in panic-related behavior. The results highlight the involvement of SNpr and MT structures in the organization of defensive behaviors and suggest an inhibitory control of striatonigral-nigrotectal pathways during the elaboration of fear- and panic-related behavior.

Intercollicular commissural connections refine the representation of sound frequency and level in the auditory midbrain.

Connections unifying hemispheric sensory representations of vision and touch occur in cortex, but for hearing, commissural connections earlier in the pathway may be important. The brainstem auditory pathways course bilaterally to the inferior colliculi (ICs). Each IC represents one side of auditory space but they are interconnected by a commissure. By deactivating one IC in guinea pig with cooling or microdialysis of procaine, and recording neural activity to sound in the other, we found that commissural input influences fundamental aspects of auditory processing. The areas of nonV frequency response areas (FRAs) were modulated, but the areas of almost all V-shaped FRAs were not. The supra-threshold sensitivity of rate level functions decreased during deactivation and the ability to signal changes in sound level was decremented. This commissural enhancement suggests the ICs should be viewed as a single entity in which the representation of sound in each is governed by the other.

Inhibition of dendritic L-type calcium current by memantine in frog tectum.

UNLABELLED: The aim of the study was to explore the effects of memantine on responses elicited in the frog tectum by the bursts of spikes of moderate strength of a single retina ganglion cell and to gain an insight about the effect of memantine on the L-type Ca(2+) current. MATERIAL AND METHODS: The experiments were performed in vivo on adult frogs (Rana temporaria). An individual retina ganglion cell (or its retinotectal fiber) was stimulated by current pulses delivered through a multichannel stimulating electrode positioned on the retina. Responses to the discharge of a single retinal ganglion cell were recorded in the tectum by an extracellular carbon-fiber microelectrode positioned in the terminal arborization of the retinotectal fiber in the tectum layer F. The solution of memantine (1-amino-3,5-dimethyladamantane) hydrochloride (30 or 45 µM) was applied onto the surface of the tectum by perfusion at a rate of 0.4 mL/min. RESULTS: Memantine (30-45 µM) largely inhibited the L-type Ca(2+) channel-mediated slow negative wave and late discharges seen in the tectum responses without any effect on fast synaptic retinotectal transmission. CONCLUSIONS: Our results suggest that the neuroprotective effect of memantine could arise not only through the inhibition of the NMDA receptor current but also through the suppression of the L-type Ca(2+) current.

Phasic nicotinic potentiation of frog retinotectal transmission enhances intrinsic activity of tectum column.

It is well established that cholinergic modulation of functioning of neuronal networks is common in the central nervous system at all scales from neuronal columns to large nuclei. It is involved in various attentional, cognitive and behavioral performances. We have recently demonstrated that a frog retinotectal transmission exhibits after-burst (phasic) potentiation caused by activation of presynaptic nicotinic receptors. We show in the present study that the phasic potentiation of the retinotectal transmission enhances activity of the tectum column by increasing dendritic L-type calcium current, and excitation of recurrent pear-shaped neurons of the column. This enhancement lasts for tens of seconds and may provide the mechanism of animal alertness.

Frog retinal ganglion cells projecting to the tectum layer F release acetylcholine as co-mediator.

Neurons may release more than one classical neurotransmitter (co-mediator). It has been demonstrated in a recent study that a burst of action potentials in frog retina ganglion cells induces an after-burst increase (phasic potentiation) of the retinotectal transmission that lasts tens of seconds. This increase is mediated by presynaptic nicotinic acetylcholine receptors that are activated by the endogenous acetylcholine released during the burst of action potentials of the retinotectal fiber. The objective of the present study was to find out the origin of acetylcholine release. We show that reduction of the retinotectal transmission to the subthreshold level by application of moderate concentrations of kynurenic acid or CNQX had no effect on the phasic nicotinic potentiation of the retinotectal transmission. This demonstrates that the retinotectal terminals are the source of acetylcholine - responsible for the phasic potentiation of retinotectal transmission. The acetylcholine is thus co-released with glutamate.

Muscarinic inhibition of recurrent glutamatergic excitation in frog tectum column prevents NMDA receptor activation on efferent neuron.

It is widely recognized that neuronal network activity can be modulated via activation of nicotinic and muscarinic acetylcholine receptors located pre- and postsynaptically. It was established in our earlier study that the activation of presynaptic nicotinic receptors greatly facilitates the retinotectal glutamatergic transmission. In the present study, we have determined a transmitter of tectal recurrent excitation and explored the effects of muscarinic acetylcholine receptor activation on the recurrent excitation and the activity of frog tectum column in vivo. Discharge of a single retinal ganglion cell was elicited by a minimal electrical stimulation of the retina. Evoked activity of the tectum column was recorded using the carbon-fiber microelectrode inserted into the tectum layer F. We found the following: 1. The recurrent excitation in the tectum column was not affected by d-tubocurarine (10 µM) and was greatly depressed by the kynurenic acid (500 µM), demonstrating glutamatergic nature of the recurrent excitation. 2. The glutamatergic recurrent excitation was largely reduced by carbamylcholine (100 µM) and oxotremorine-M (10 µM), demonstrating that the activation of muscarinic receptors, located, presumably, on the presynaptic terminals of recurrent pear-shaped neurons, inhibits the recurrent excitation in the tectum column. 3. The muscarinic inhibition of glutamatergic recurrent transmission had critical influence on the activity of the tectum column, preventing the generation of an output signal through suppression of the NMDA receptor activation and establishing necessary conditions for returning of the network to its resting state.

The organization of CRF neuronal pathways in toads: Evidence that retinal afferents do not contribute significantly to tectal CRF content.

Previous work has suggested that the peptide corticotropin-releasing factor (CRF) acts to inhibit visually guided feeding in anurans, but little is known about potential targets for CRF within the subcortical visuomotor circuitry. Here we investigated the relationship between CRF neuronal organization and visual pathways in toads. CRF-immunoreactive (ir) neurons and fibers were widely distributed throughout the ventral subpallial telencephalon and hypothalamus, although few fibers were found in telencephalic areas, such as the striatum, that are known to project to the tectum in anurans. Large populations of CRF-ir cells were observed in the bed nucleus of the stria terminalis and preoptic area as well as in the ventral infundibular hypothalamus. CRF-ir neurons and fibers also were observed in several midbrain and brain stem areas. Colchicine treatment significantly enhanced CRF-ir neurons and fibers throughout the brain, and revealed CRF-ir cell groups in several brain areas (including the dorsal hypothalamus) that were not observed in untreated animals. Intrinsic CRF-immunoreactive neurons were routinely observed in cell layer 8 and sometimes in layer 6 of the optic tectum in both untreated and colchicine-treated animals. CRF was detected in toad optic tectum by radioimmunoassay, although tectal CRF content was less than that of the hypothalamus and forebrain. Unilateral eye ablation did not affect CRF content of the contralateral optic tectum. We conclude that CRF-producing neurons are widely distributed in several areas of the toad brain known to be involved in regulating the behavioral, autonomic and endocrine response to stressors, including the optic tectum and several brain areas known to project to the optic tectum. Furthermore, retinal afferents do not contribute significantly to tectal CRF content.

Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system.

BACKGROUND: Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits. RESULTS: Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-alpha on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-alpha resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-alpha treatment also enhanced the overall growth of tectal cell dendrites. Finally, we found that TNF-alpha-reared tadpoles had increased susceptibility to pentylenetetrazol-induced seizures. CONCLUSIONS: Taken together our data are consistent with a model in which TNF-alpha causes premature stabilization of developing synapses within the tectum, therefore preventing normal refinement and synapse elimination that occurs during development, leading to increased local connectivity and epilepsy. This experimental model also provides an integrative approach to understanding the effects of cytokines on the development of neural circuits and may provide novel insights into the etiology underlying some neurodevelopmental disorders.

The unconditioned fear produced by morphine withdrawal is regulated by mu- and kappa-opioid receptors in the midbrain tectum.

We have recently shown that morphine withdrawal sensitizes the neural substrates of fear in the midbrain tectum structures--the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC). In the present study, we investigated the role of mu- and kappa-opioid receptors in the mediation of these effects. Periadolescent rats chronically treated with morphine (10 mg/kg; s.c.) twice daily for 10 days were implanted with an electrode glued to a guide-cannula into the dPAG or the IC. Forty-eight hours after the interruption of this treatment, the effects of intra-dPAG or intra-IC microinjections of [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO; 0.6 and 1 nmol/0.2 microl)--a selective mu-receptor agonist--or nor-binaltorphimine (BNI; 2.5 and 5 microg/0.2 microl)--a selective kappa-receptor antagonist with tardive action--on the freezing and escape thresholds determined by electrical stimulation of the dPAG and the IC were examined. For both structures, morphine withdrawal produced pro-aversive effects. DAMGO and BNI had antiaversive effects when injected into the dPAG and IC of non-dependent rats. In morphine-withdrawn rats, only BNI continued to promote antiaversive effects in both structures. Whereas DAMGO lost its antiaversive efficacy when injected into the dPAG, only its highest dose promoted antiaversive effects in the IC of morphine-withdrawn rats, suggesting the development of an apparent tolerance. Thus, the enhanced reactivity of the midbrain tectum in morphine-withdrawn periadolescent rats may be due, at least partially, to an impairment of the inhibitory influence of mechanisms mediated by mu-receptors on the neural substrates of fear in this region.

Disappearance of gadolinium enhancement in a chemoresistant astrocytoma of the tectum after high-dose interferon beta.

Interferon beta 6 million units per week was administered to a patient with an aggressive astrocytoma in the tectum that was resistant to cisplatin, etoposide, vinblastine, and the oral alkylating agent temozolomide. The tumor was immunopositive for O6-methylguanine-DNA methyltransferase (MGMT). Interferon beta caused the disappearance of the gadolinium-enhanced lesion in the tectum. Interferons have apoptotic and antiangiogenic effects on tumor cells, and the lesion's disappearance may have been induced by complexes of these effects. Administration of interferon beta might have a favorable effect on tectal gliomas that are immunopositive for MGMT and resistant to chemoradiotherapy including temozolomide.

Brainstem areas activated by diazepam withdrawal as measured by Fos-protein immunoreactivity in rats.

In the 1970s, chronic treatment with benzodiazepines was supposed not to cause dependence. However, by the end of the decade several reports showed that the interruption of a prolonged treatment with diazepam leads to a withdrawal syndrome characterized, among other symptoms, by an exaggerated level of anxiety. In laboratory animals, signs that oscillate from irritability to extreme fear-like behaviors and convulsions have also been reported. In recent years many studies have attempted to disclose the neural substrates responsible for the benzodiazepines withdrawal. However, they have focused on telencephalic structures such as the prefrontal cortex, nucleus accumbens and amygdala. In this study, we examined the Fos immunoreactivity in brain structures known to be implicated in the neural substrates of aversion in rats under spontaneous diazepam-withdrawal. We found that the same group of structures that originally modulate the defensive responses evoked by fear stimuli, including the dorso-medial hypothalamus, the superior and inferior colliculus and the dorsal periaqueductal gray, were most labeled following diazepam withdrawal. It is suggested that an enhanced neural activation of neural substrates of fear in the midbrain tectum may underlie the aversive state elicited in diazepam-withdrawn rats.

Functional and ultrastructural neuroanatomy of interactive intratectal/tectonigral mesencephalic opioid inhibitory links and nigrotectal GABAergic pathways: involvement of GABAA and mu1-opioid receptors in the modulation of panic-like reactions elicited by electrical stimulation of the dorsal midbrain.

In the present study, the functional neuroanatomy of nigrotectal-tectonigral pathways as well as the effects of central administration of opioid antagonists on aversive stimuli-induced responses elicited by electrical stimulation of the midbrain tectum were determined. Central microinjections of naloxonazine, a selective mu(1)-opiod receptor antagonist, in the mesencephalic tectum (MT) caused a significant increase in the escape thresholds elicited by local electrical stimulation. Furthermore, either naltrexone or naloxonazine microinjected in the substantia nigra, pars reticulata (SNpr), caused a significant increase in the defensive thresholds elicited by electrical stimulation of the continuum comprised by dorsolateral aspects of the periaqueductal gray matter (dlPAG) and deep layers of the superior colliculus (dlSC), as compared with controls. These findings suggest an opioid modulation of GABAergic inhibitory inputs controlling the defensive behavior elicited by MT stimulation, in cranial aspects. In fact, iontophoretic microinjections of the neurotracer biodextran into the SNpr, a mesencephalic structure rich in GABA-containing neurons, show outputs to neural substrate of the dlSC/dlPAG involved with the generation and organization of fear- and panic-like reactions. Neurochemical lesion of the nigrotectal pathways increased the sensitivity of the MT to electrical (at alertness, freezing and escape thresholds) and chemical (blockade of GABA(A) receptors) stimulation, suggesting a tonic modulatory effect of the nigrotectal GABAergic outputs on the neural networks of the MT involved with the organization of the defensive behavior and panic-like reactions. Labeled neurons of the midbrain tectum send inputs with varicosities to ipsi and contralateral dlSC/dlPAG and ipsilateral substantia nigra, pars reticulata and compacta, in which the anterograde and retrograde tracing from a single injection indicates that the substantia nigra has reciprocal connections with the dlSC/dlPAG featuring close axo-somatic and axo-dendritic appositions in both locations. In addition, ultrastructural approaches show inhibitory axo-axonic synapses in MT and inhibitory axo-somatic/axo-axonic synapses in the SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms in the cranial aspects of the MT as well as in the mesencephalic tegmentum, offer a neuroanatomical basis of a pre-synaptic opioid inhibition of GABAergic nigrotectal neurons modulating fear in defensive behavior-related structures of the cranial mesencephalon, in a short link, and through a major neural circuit, also in GABA-containing perikarya and axons of nigrotectal neurons.

[Taurine effects on background impulse activity of the internal geniculate body neurons and mesencephalic inferior tubers of white rats]. / Vliianie taurina na fonovuiu impul'snuiu aktivnost' neironov vnutrennogo kolenchatogo tela nizhnikh bugrov chetverokholmiia belykh krys.

Microelectrophysiological and computer techniques were used in the study of background impulse activity (BIA) of the internal geniculate body (IGB) neurons and mesencephalic inferior tubers (MIT) of white rats. Definite differences were found in BIA by regularity, dynamic types and modality of interimpulse histograms. Mean frequency of MIT neuron discharges was 16-17 Hz and was about 3 times higher than in neurons of the IGB. Intraperitoneal injection of taurin noticeably suppressed neuronal activity in both nuclei. The drug reduced mean frequency of background impulse discharges both in MIT and IGB. Thus, taurin produces primarily suppressing modulating effect on neuronal activity of IGB and MIT.

Regulation of ipsilateral visual information within the tectofugal visual system in zebra finches.

The eyes of zebra finches are placed laterally, the foveae are looking into different directions. It is unlikely that the birds are able to process different images from both eyes simultaneously. A neural mechanism might therefore be necessary to guide the birds' attention to one of the two eyes and to reduce the processing of information of the other. Previous studies revealed that information from the ipsilateral eye is indeed suppressed on its way to the telencephalon by the activity of the contralateral eye. It has been suggested that two nuclei of the tecto-thalamic tract, nucleus subpraetectalis and nucleus interstitio praetecto subpraetectalis, are a central part of such a suppressive mechanism. Using electrophysiological recordings, we investigated the influence of these two nuclei and nucleus rotundus on the processing of binocular visual information by treating the nuclei with picrotoxin or electrolytic lesions. Deactivation of inhibitory neurons within SP/IPS leads to a significant increase of the ectostriatal responses to ipsilateral and bilateral stimulation, the responses to contralateral stimulation remain unaffected. Lesioning SP/IPS does not alter the responses to visual stimuli. Treatment of nucleus rotundus with picrotoxin increases contralaterally and bilaterally, but not ipsilaterally evoked responses. A wiring diagram is presented which interprets these findings.

Epileptic discharge of cortical, subcortical and spinal neurons in penicillin induced experimental epilepsy.

The sensitivity and electrophysiological patterns of paroxysmal activity induced in different brain structures by topical application of penicillin-G were evaluated in the rat. Recordings were carried out in five groups of animals, in telencephalon, diencephalon, mesencephalon, rombencephalon and spinal cords. The following analysis were carried out: frequency distribution histograms, latency and time course duration of paroxysmal activity, duration and amplitude of epileptic bursts. The results obtained showed that the nervous structures tested with penicillin-G had a different epileptogenic sensitivity and response pattern which significantly changed along the cerebral cortex-spinal cord axis. The highest epileptic sensitivity was observed in somatosensory cortex (SI) at 500-600 microns depth; in the other cortical layers, a significant lenghtening in latency was observed. Among the other structures, the spinal cord seemed to be the most sensitive target to the epileptogenic action of penicillin-G, whereas in the remaining structures, sensitivity significantly decreased in rostro-caudal direction. As far as the features of the paroxysmal activity are concerned, significant differences among tested structures were observed. In particular, within the SI cortex, the main differences were represented by the gradual increase in burst frequency and voltage from the surface to the IVth layer and by their subsequent decrease in deeper layers (V-VI). In the diencephalon, the paroxysmal activity was similar to that observed in more superficial and deeper cortical layers even though epileptic bursts showed a lower amplitude. Mesencephalon and rombencephalon displayed a paroxysmal activity with a distinctive feature, characterized by long lasting bursts of low amplitude, although bulbar outbursts showed a shorter duration than the mesencephalic ones. In the spinal cord, the epileptiform activity displayed a different paroxysmal pattern, characterized by the longest duration and the highest amplitude. The different sensitivities of the investigated brain structures to penicillin-G and the characteristics of the induced paroxysmal activity have been extensively discussed.