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M A Corner

Publications and source records attributed to M A Corner.

18 recordsLinked to original sources
PubMed1992

Spontaneous firing as an epigenetic factor in brain development--physiological consequences of chronic tetrodotoxin and picrotoxin exposure on cultured rat neocortex neurons.

Functional consequences of either suppressing or intensifying spontaneous neuronal firing have been studied in developing rat cerebral cortex cultures using, respectively, tetrodotoxin (TTX) and picrotoxin (PTX) added chronically to the growth medium. Simple measures derived from the interspike interval histogram were able to powerfully discriminate between age and treatment groups. After return to control medium, most TTX-treated neurons spontaneously displayed stereotyped clustering of action potentials ('phasic' firing) which closely resembled the characteristic firing patterns seen acutely in the presence of PTX. The 'TTX-syndrome' thus suggests that GABAergic synaptic inhibition is ineffective in cortical networks grown under conditions which prevent the expression of bioelectric activity. In contrast, after return to control medium, neurons which had been partially disinhibited throughout development (by continuous exposure to PTX) had even less phasic firing than was measured in age-matched controls. Based upon these and previous findings, a two (main) factor model is put forth which can economically account for the major effects. The working hypothesis embodied in this model is that phasic neuronal discharges not only accelerate the maturation of excitatory connections within the neocortex but, even more important, are crucial for the development of adequate inhibitory synaptic transmission.

Animals↗
PubMed1992

The emergence of long-lasting transients of activity in simple neural networks.

The question was investigated whether long-lasting transients of activity, observed to occur in the intact cerebral cortex (EEG slow (delta) waves and 'K' complexes) as well as in isolated tissues cultured in vitro, can also emerge in a model network of excitatory and inhibitory cells. We show that such transients can indeed occur even if the cells do not have built-in slow kinetics. For certain parameter settings, the network is in a bistable state in which periods of increased activity (long-lasting transients) alternate with minimal activity. Transients are triggered by spontaneously firing cells ('noise'), which, rather than via a build-up of recurrent synaptic inhibition, also initiate their termination. During a transient, the network continually makes transitions from one equilibrium to another as a result of spontaneous firing until it is switched back to the quiescent state, i.e., after a variable period of time of noise-induced transitions the transient is terminated. If the network is small, activity can terminate even without inhibition. In large networks, inhibition keeps the network sensitive to spontaneously firing cells by holding it in the neighbourhood of a critical point between active and quiescent state.

Action Potentials↗
PubMed1992

Effects of spontaneous bioelectric activity and gangliosides on cell survival in vitro.

Chronic suppression of spontaneous bioelectric activity in spinal cord explants in the presence of tetrodotoxin (TTX) during network formation caused a large reduction in cell number (lowered DNA levels). The addition of gangliosides failed to protect against this cell loss. Conversely, the omission of galactose from the growth medium had no effect on DNA levels. It was concluded that the presence or absence of afferent selectivity is unlikely to require the survival of a regionally specific subpopulation of preferred dorsal root ganglion target cells. Neocortical explants also showed a large reduction in DNA levels following chronic TTX treatment, and morphometric analysis confirmed that neuronal survival was affected to the same degree. Chronic ganglioside supplementation failed to influence DNA and cell counts in either control or TTX-treated explants, but one of the added gangliosides (GD1a) stimulated extensive neuritic outgrowth in electrically silenced cultures. Particular ganglioside species, therefore, may exert a growth stimulating influence that can partially compensate for the absence of bioelectric self-stimulation during early development.

Animals↗
PubMed1992

Spike-train analysis reveals "overshoot" in developing rat prefrontal cortex function.

A multivariate analysis of spontaneous single neuron firing in the developing prefrontal cortex (PFC) of urethane anesthetized rats has been made using selected spike-train parameters. In particular, the development of modal interspike intervals closely paralleled the volumetric 'overshoot' reported earlier by us for rat PFC. Thus, the growth phase is characterized by progressively higher firing rates associated with longer modal intervals (i.e., a change from phasic to tonic firing, suggestive of increasingly effective inhibition). In contrast, the subsequent abrupt reduction in PFC volume is accompanied by the appearance of extremely short interspike intervals with no concomitant change in overall mean discharge rates ('burst' firing). This last development could be largely due to the 'pruning' of excessive excitatory synaptic contacts.

Action Potentials↗
PubMed1991

Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801.

In order to study the involvement of NMDA-receptor activation in brain development, rat pups were chronically treated with the non-competitive NMDA antagonist MK-801 during the neonatal period. We recorded the cortical EEG at various vigilance states throughout the treatment period. Spectral analysis of the EEG showed reduced power in the delta (delta) frequency range (1.5-4 Hz) during quiet sleep and less power in the theta (theta) range (4-7 Hz) during REM-sleep in MK-801 animals than in controls. No significant differences were found for the total time spent in each of the different vigilance states. We conclude that chronic MK-801 treatment probably causes a developmental retardation in state-related brain activities.

Animals↗
PubMed1991

Abnormalities in the spontaneous firing patterns of cultured rat neocortical neurons after chronic exposure to picrotoxin during development in vitro.

We have used the GABA-A antagonist picrotoxin (PTX) to investigate whether chronic disinhibition, leading to intensified neuronal firing, would induce a specific pattern of physiological alterations in cultured rat neocortex cells. Overall mean spontaneous discharge rates were little affected by 1 microM PTX but firing occurred mainly as repetitive high-frequency bursts of action potentials. This "phasic" pattern contrasted with the irregular, quasi-random, firing usually seen in control units. Neurons tested in normal growth medium after prolonged exposure to 1 microM PTX showed weaker interspike interval dependencies (Markov value) than in controls, along with reduced regularity in the occurrence of bursts. Since all physiological changes were opposite in direction to those reported earlier after chronic suppression of bioelectric activity, the results support the hypothesis that endogenous synaptic and/or action potentials are important for the maturation of neocortical networks. Since experimental alterations were found only in spike-train parameters which reflect ontogenetic changes in untreated control cultures, GABAergic inhibition (by preventing neuronal discharges from becoming too intense) presumably serves to constrain the rate of development within optimal limits.

Action Potentials↗
PubMed1991

Developmental changes in B-50 (GAP-43) in primary cultures of cerebral cortex: content and phosphorylation of B-50.

The content and phosphorylation of the neuronal growth-associated protein B-50 (GAP-43) were studied in cultured neocortex as a function of normal development and development in the presence of tetrodotoxin (TTX), a blocker of bioelectric activity (BEA). The observations were correlated with previous morphological findings on neurite outgrowth and B-50 immunolocalization in the same cultures. In control cultures, the concentration of B-50 reached a maximum at 7 days in vitro (DIV) and decreased thereafter, whereas the concentration of neuron specific enolase (NSE), which was used as a neuronal reference marker, rose till 28 DIV and leveled off towards 42 DIV. The degree of basal phosphorylation of B-50 (relative to that of total protein) decreased after the first week in vitro. Stimulation of B-50 phosphorylation by phorbol ester also decreased with age in vitro, indicating that changes in B-50 phosphorylation were mainly due to changes in protein kinase C (PKC) activity. The chronic presence of TTX led to a reduced content of B-50 and NSE after 14 DIV. The basal phosphorylation of B-50 was neither affected by acute nor chronic TTX treatment. However, upon stimulation of PKC with phorbol esters, some alterations of B-50 phosphorylation were revealed in cultures grown in TTX. These biochemical observations are in line with the absence of effects of TTX on neurite outgrowth during the first 2 weeks in culture, and later effects of TTX on neuronal survival. The developmental changes in B-50 concentration and phosphorylation largely correlate with previous morphological observations on axonal outgrowth and growth cone shape in the same cultures. We suggest that B-50 phosphorylation plays an important role in transducing extracellular signals into directed neurite outgrowth.

Animals↗
PubMed1990

Development in the absence of spontaneous bioelectric activity results in increased stereotyped burst firing in cultures of dissociated cerebral cortex.

Quantitative analysis of neuronal firing patterns was used to study the effects of chronic suppression of bioelectric activity (BEA) on functional development in primary cultures of fetal rat cerebral cortex. BEA was monitored with extracellular electrodes in active control cultures or, after return to control medium, in cultures chronically silenced with tetrodotoxin (TTX) at around 7, 14, 21 and 42 days in vitro. Spike trains of single neurons lasting up to 25 min duration were analyzed using a previously published set of computer programs. In control cultures, the main developmental trends seen in a previous study could be replicated. After development in the presence of TTX, activity levels were increased at all ages, and a high incidence was found of a single firing pattern characterized by stereotyped burst firing, while showing a low minute order variability in firing rate and low dependencies between successive intervals; conversely, the incidence of variable/non-burst firing was decreased relative to untreated cultures. The former firing pattern (i.e. non-variable bursting) could also be produced through acute addition of the GABA (A)-antagonist picrotoxin to control cultures, and resembled interictal burst firing observed in models of chronic epilepsy in vivo. These similarities suggest that chronic silencing of the cultures may have resulted in a functional disinhibition of the neuronal network; such disinhibition might be related to the increased cell death which we observed with chronic TTX-treatment in the same cultures.

Action Potentials↗
PubMed1978

Topography of cutaneous mechanoreceptive neurones in dorsal root ganglia of skin-grafted frogs.

1. Topographical distribution patterns of dorsal root ganglion (d.r.g.) cutaneous neurones providing innervation to various body surfaces were examined in doublypithed Discoglossus pictus frogs.2. Using electrophysiological methods, sensory neurones innervating back skin were observed to predominate on the dorsal ganglionic surfaces, while belly skin neurones were most prevalent in the caudal half of the d.r.g. ventral surfaces. Flank neurones clustered in the medial half of d.r.g. ventral surfaces.3. Cutaneous neuronal distribution patterns within the d.r.g. of 180 degrees skin grafted animals were indistinguishable from those observed in control frogs.4. Sensory neurone distribution patterns were found to be altered in all animals with single skin type grafts. Projection patterns were always heaviest towards the autograft, which was on the opposite body surface (i.e. dorsally located d.r.g. sensory neurones projected to back skin on the frog's ventrum, while ventrally located neurones projected to belly skin on the frog's dorsum).5. The results are discussed in the light of several selective outgrowth mechanisms which have been proposed as a possible underlying basis for the development of misdirected wiping reflex behaviour in skin grafted anurans. The findings indicate that none of the proposed selective growth mechanisms can account adequately for the development of misdirected wiping reflexes, at least in the species studied.6. It is suggested that selective cell replacement, based upon competition among prespecified cutaneous neurones, might best account for the development of normal and misdirected wiping reflexes in frogs.

Action Potentials↗
PubMed1977

Effect of cutaneous stimulation on the development of misdirected wiping reflexes in skin-grafted Discoglossus pictus.

The frog, Discoglossus pictus, has been studied with respect to wiping reflex behavior developing after skin rotations performed at larval stages. Misdirected wiping reflexes were obtained only from belly skin-grafts placed on the animals' back; back skin-grafts on the belly failed to elicit any misdirected limb movements in this species. We found that misdirected reflexes occurred more readily in 3-week and older animals if not subjected to any previous test experience, than in younger naive frogs. Frogs that had been exposed to daily cutaneous stimulation between 2 to 4 weeks after metamorphosis showed a delayed development of misdirected responses.

Age Factors↗
PubMed1976

Cyclic EEG and motility patterns during sleep in restrained infant rats.

When restrained in a quasi-fetal position, infant rats (2--3 weeks old) remain for an extended period in a sleep-like state as judged by polygraphic criteria. Moreover, they become very difficult to arouse by sensory stimuli, and show a level of spontaneous motility considerably higher than is normally found at this age during sleep. Phasic generalized body movements, which are often quite stereotyped, occur in trains at regular intervals, against a low background level of neck muscle tonus. The amplitude of the cortical EEG, especially in the delta band, is negatively correlated with the frequency of spontaneous motor burst activity. It is suggested that these REM-like "rapid body movements" in immature mammals may well represent a transitional stage between fetal behavior patterns and sleep motility in the adult organism.

Age Factors↗
PubMedDate not supplied

Cutaneous receptive field enlargement following skin-grafting in the frog, D. pictus.

Misdirected wiping responses occur in Discoglossus pictus frogs when skin-grafted early in larval life. Cutaneous receptive fields (CRF) for various peripheral nerve branches were mapped electrophysiologically in control and skin-grafted frogs. The ventrolateral nerve branch (VL) frequently provided innervation for significant areas of dorsal skin in both control and skin-grafted animals. Although the VL crossed over onto dorsal skin areas in some skin-grafted frogs giving rise to misdirected reflexes, these dorsal extensions frequently failed to include all skin areas from which the maladaptive reflexes could be elicited. It was concluded that misdirected reflexes are mediated via dorsal nerve branches occupying normal mid-dorsal areas of the back.

Abdomen↗
PubMedDate not supplied

Receptive fields of cutaneous mechanoceptive neurons in the frog, Discoglossus pictus, following skin transplantation at larval stages.

The receptive fields of individual spinal ganglion cells were mapped in frogs in which a large patch of belly skin had been transplanted to the back prior to metamorphosis. Wiping reflexes aimed at the belly could be elicited both from regenerated normal and transplanted belly skin. We concluded that the sensory neurons mediating misdirected responses could not be the same ones as those mediating normal wipes, since unit receptive fields were either on normal or on grafted belly skin, but never both. A proposed mechanism for explaining the origin of cutaneous reflex connections on the basis of selective innervation of peripheral tissues could hereby be discarded.

Animals↗