Biomedical subjects

M A Corner

Publications and source records attributed to M A Corner.

At least 37 records · Page 2Linked to original sources

PubMed1987

Central neuronal responsiveness to sensory ganglion stimulation is correlated with the incidence of spontaneous bioelectric activity in developing spinal cord cultures.

In spinal cord explants co-cultured with dorsal root ganglion cells for 3-4 weeks in a (horse)serum-containing medium, the spread of ganglion-evoked action potentials from monosynaptic innervation sites ("polysynaptic excitability index") was not correlated with the incidence of neuronal "background" discharges. Moreover, chronic exposure of serum-grown cultures to tetrodotoxin (TTX) in a dose sufficient to reversibly block bioelectric activity, failed to significantly affect this index. For explants grown in a chemically defined medium (CDM) similar excitability scores were obtained only if a low level of spontaneous activity was measured. The most active preparations scored considerably higher, with intermediate values being found in the moderately active cultures. Chronic TTX-exposure in developing CDM-grown cultures reduced their excitability scores to the level found in weakly active, untreated, explants despite a normal incidence of spontaneous activity. The present study indicates that low levels of spontaneous activity in untreated explants were associated with a similar sluggishness of DRG-evoked responses as previously observed after chronic treatment with TTX. These results give additional grounds for confidence that this reduced responsiveness of spinal cord neurons to sensory input is indeed attributable to prolonged reduction of centrally generated excitation during development in vitro.

Aging↗

PubMed1987

Indications for a critical period for synapse elimination in developing rat cerebral cortex cultures.

It was observed in an earlier study that chronic tetrodotoxin (TTX) blockade of spontaneous bioelectric activity (SBA) in rat cerebral cortex cultures prevented the large-scale elimination of synapses which normally occurs during the fourth week in vitro. This prompted us to study whether the persisting high synapse density during long-term TTX-treatment would still return to the "normal' low level after restoration of SBA. Therefore, cultures grown in TTX-supplemented medium for 5 weeks were switched to control medium for an additional week prior to fixation. Electron microscopic analysis showed that the numerical synapse density remained at a high level, thus suggesting the presence of a critical period whereafter bioelectrically controlled elimination of redundant connections no longer occurs. In contrast, the mean size of synaptic structures depended only on the functional state of the tissue at the moment of fixation, being larger in TTX-silenced cultures than in bioelectrically active ones regardless of treatment during the first 5 weeks in vitro.

Animals↗

PubMed1986

Some functional effects of suppressing bioelectric activity in fetal mouse spinal cord-dorsal root ganglion explants.

Organotypic explants of fetal mouse spinal cord-dorsal root ganglia were grown for 3 weeks in the presence of 10 mM magnesium ion, which effectively eliminated all recordable bioelectric activity throughout the culturing period. When tested in minimal essential medium, the chronically silenced explants had significantly fewer points from which spontaneous neuronal activity could be recorded. In addition, fewer points could be found that showed dorsal root ganglion-evoked responses, resulting from a greater tendency for the spinal cord activity to be restricted to the vicinity of the dorsally entering DRG fibers. These findings, therefore, support the hypothesis that spontaneous bioelectric activity is required for functional as well as structural maturation of neural networks.

Animals↗

PubMed1984

Postnatal development of spontaneous neuronal discharges in the pontine reticular formation of free-moving rats during sleep and wakefulness.

A developmental study has been made of spontaneous neuronal activity within the pontine reticular formation (giant cell field: FTG) of the rat between one week and one month after birth. Through day 14, the recorded FTG neurons discharged more frequently during quite sleep (QS) than was generally true in older animals. In addition, they were active to the same extent during active-sleep (AS) as during waking-with-movements (AW). In contrast, most of the cells recorded from day 15 on were considerably more active during AS and AW, relative to the QS level, than had hitherto been the case. This new class of neurons, in turn, fell into two sub-groups, one of which was most active during AW while the other was more active during AS. Clomipramine selectively suppressed AS along with the neuronal activity patterns associated with it, and in many cases the QS firing level was even lower than it had been prior to the injection. It is concluded that FTG unit activity is an excellent monitor for controlling the effectiveness of experimental manipulations of AS but is probably not involved in its generation.

Aging↗

PubMed1984

Effects of chronic suppression of bioelectric activity on the development of sensory ganglion evoked responses in spinal cord explants.

Dorsal root ganglion (DRG) afferent terminals were identified, using electrophysiological techniques, within fetal mouse spinal cord cross-sections cultured in vitro. Afferent distribution patterns were monitored in explants grown for 3 to 6 weeks either in a serum-supplemented or in a serum-free, chemically defined medium (CDM). Bioelectrically active control explants from both series were compared with explants which had been reversibly silenced by chronic exposure to tetrodotoxin (TTX). The control (serum-grown) cultures showed a significant dorsal cord innervation preference, whereas in the corresponding TTX series there was an equal dorsoventral distribution. In the CDM series the mean number of DRG evoked responses was lower at first in TTX-grown than in control cultures, but with age in vitro there was a rise in excitability to normal levels. Spontaneous neuronal activity was abnormally low in cultures (serum as well as CDM-grown) which had been exposed to TTX. It is concluded that bioelectric activity may be an important factor in the proper regulation of synaptic connectivity and functional responsiveness in the developing spinal cord.

Animals↗

PubMed1983

Effects of chemical additives on functional innervation patterns in mouse spinal cord-ganglion explants in serum-free medium.

The distribution of sensory evoked bioelectric activity was examined in spinal cord-dorsal root ganglion (SC-DRG) preparations cultured in a chemically defined, serum-free medium (CDM). DRG afferents showed no preferential innervation of dorsal cord regions in this CDM, on the basis of electrophysiological mapping of the distribution of evoked responses at 4 weeks in vitro. Addition of chondroitin sulfate, galactose-1-phosphate or D(+)-galactose (but not glucose-1-phosphate) to the CDM resulted in a significant increase in presumed monosynaptic connections within the dorsal cord, thus mimicking the results observed in serum-supplemented medium [1,6]. Inasmuch as D(+)-galactose bears no negative charges yet restores the selective functional innervation, whereas glucose-1-phosphate (a highly charged molecule) fails to do so, it is concluded that it is galactose utilization, rather than the charged nature of the chondroitin sulfate and galactose-1-phosphate molecules, which is responsible for the effect.

Animals↗

PubMed1983

Pharmacological suppression of REM sleep prior to weaning counteracts the effectiveness of subsequent environmental enrichment on cortical growth in rats.

Male Wistar rat pups were deprived of REM sleep by means of daily injections of clonidine between 8 and 21 days after birth. From day 28 they were reared under either 'enriched' or 'standard' environmental conditions. At 75 days of age the animals were sacrificed, and the regional brain weights were compared with two (differentially reared) control groups. Whereas cortical weight was greater in the enriched than in the standard control rats, no differences were found between the corresponding REM sleep-deprived (i.e. clonidine-treated) groups. These results suggest that REM sleep deprivation and/or disturbances of central noradrenergic function during early development can counteract growth responses of the brain to environmental stimulation later in life.

Animals↗

PubMed1982

Influence of growth medium, age in vitro and spontaneous bioelectric activity on the distribution of sensory ganglion-evoked activity in spinal cord explants.

The role of serum added to the culture medium and of spontaneous bioelectric activity in the development of sensory afferent connections was studied, employing fetal mouse spinal cord explants with attached dorsal root ganglia (DRG) as an in vitro model system. Afferent DRG terminals in the cord explants were localized on the basis of 'fixed-latency' DRG-evoked action potentials, which were anatomically verified in several experiments using horseradish peroxidase histology. In serum-supplemented medium (HSSM), but not in chemically defined medium (CDM), those DRG fibers which grew into the dorsal side of the cord terminated predominantly within the dorsal cord region, and remained there throughout the experimental period (18-33 days in vitro). In contrast, ventrally entering fibers terminated equally in both the dorsal and the ventral cord regions in young cultures (18-24 days in vitro) but were no longer observed after 27 days in vitro. Cultures grown in HSSM with the addition of xylocaine, in order to chronically suppress spontaneous bioelectric activity, essentially corresponded (at 25-32 days in vitro) to the picture seen in the control series at the same age. On the basis of polysynaptic DRG-evoked responses in the cord, developmental changes in local neuronal networks were inferred which resulted in less spread of DRG-evoked activity with age in HSSM, and more spread with age in CDM-grown cultures. It is concluded that for the formation of selective DRG connections in the spinal cord: (i) a serum-borne factor plays a role: and (ii) functional activity is not required.

Animals↗

PubMed1981

Suppression of active sleep by chronic treatment with chlorimipramine during early postnatal development: effects upon adult sleep and behavior in the rat.

In an attempt to study the possible role of active sleep in brain development, male rats were injected twice daily with chlorimipramine, a potent monoamine reuptake blocker, from 1 week to 3 weeks of postnatal age. AS was reduced to less than 10% of total sleep time, the level found in mature rats. Most of the AS reduction was compensated for by quiet sleep but a slight increase in wakefulness also occurred, owing to brief interruptions of sleep at times when AS was expected. In adulthood, the AS-deprived rats showed a higher percentage of AS than did the controls, due to an increase in frequency and duration of AS epochs. Moreover, many of the epochs contained abnormally frequent and strong jerky body movements and rapid-eye-movements, reminiscent of neonatal AS patterns. In addition, the amplitude of hippocampal theta waves during AS was greater than in control rats. The chlorimipramine-treated rats also showed behavioral abnormalities in later life. On the open field test exploratory behavior was much reduced, while increased rearing and defecation occurred. Masculine sexual performance was severely deficient, primarily due to the low level of intromissions and ejaculations. Experimental animals performed less efficiently than controls on a temporal learning task (differential reinforcement of low response rate) and responded more rapidly on a spatial task (left-right alternation learning). These results demonstrate that early interference with the functioning of monoaminergic systems can have long-lasting physiological and behavioral consequences. Furthermore, they are consistent with the hypothesis that AS is an important factor in normal brain development.

Aggression↗

PubMed1981

Peripheral reinnervation patterns and dorsal root ganglion topography in skin-grafted frogs: a behavioral and histological examination.

Cutaneous respective fields for the first ventrolateral (VL1) and dorsomedial nerve trunks were mapped out behaviourally in normal and in skin-grafted Discoglossus pictus frogs. Ventrally directed wiping responses were obtained from stimulation of dorsally located belly skin grafts in all experimental animals. These misdirected responses were abolished completely by cutting either the dorsomedial nerve trunk or both the dorsomedial and the VL1 nerve trunks. The topography of cutaneous neurons of the dorsal root ganglion innervating dorsal skin areas was demonstrated by back-filling the dorsomedial nerve trunk with cobalt. In both normal and skin-grafted frogs, twice as many cobalt-filled neurons were observed in the dorsal half of the ganglion as in the ventral half although the absolute number of filled cells in different regions was the same in both groups. It was concluded that misdirected responses following skin rotation cannot be explained on the basis of a re-establishment of the original peripheral nerve connections.

Animals↗

PubMed1980