Effects of acute ethanol administration on neocortical inhibition.

The hypothesis that acutely administered ethanol could interfere with neocortical recurrent inhibition (RI) was supported. The large surface negative wave in response to antidromic stimulation of the cerebral peduncle represents a summation of inhibitory postsynaptic potentials, a measure of RI. In acute experiments on adult rats, blood alcohol levels of less than about 120 mg/100 ml slightly facilitated the surface negative wave. Higher blood alcohol levels always blocked the surface negative response. Stimulation of the somatosensory thalamic relay nuclei produced a cortical response on which ethanol had a moderate blocking effect. Conditioning-test procedures revealed that cerebral peduncle stimulation strongly blocked the thalamocortical (test) response, especially after ethanol, but thalamic stimulation (conditioning) had no effect upon the surface negative wave. This demonstrates a differential effect on the two cortical processes. Cortical RI seems to be especially sensitive to blood alcohol level, but the function of cortical RI is complex. By way of acting on RI, ethanol likely affects control of sensory input and cortical sensory organization as well as selectivity and magnitude of motor discharge.

Effects of chronic ethanol treatment on neocortex.

Neocortical inhibition and neuronal morphology were studied in rats following chronic ethanol treatment (CET). In terminal acute experiments, spontaneous neuronal discharges in pair-fed and naive rats were inhibited by epicortical stimulation, a procedure known to produce postsynaptic inhibition. Few units in CET rats were inhibited by such stimulation. Cortical recurrent inhibition, indicated by a surface-negative potential in response to antidromic stimulation of the cerebral peduncle, was little affected by a challenge dose of ethanol, compared with the response in pair-fed animals. Recurrent inhibition involves inhibitory interneurons. CET apparently made inhibitory interneurons and inhibitory postsynaptic receptors less responsive to ethanol. Apical dendritic spines on some portions of pyramidal neurons increased in number with CET. This could reflect a compensatory growth in neurons not damaged by CET. The overall observations are consistent with ethanol affecting one or more specific systems of cortical motor control as opposed to its presumed general disinhibitory effect.

Inhibition in penicillin-induced epileptic foci.

A previous study indicated that the early surface negative component (associated with recurrent inhibition) of the evoked potential recorded from cat pericruciate cortex, subsequent to pyramidal tract stimulation, was altered after application of penicillin to the cortical surface (Van Duijn et al. 1973). This suggested that decreased effectiveness of recurrent inhibition might be the basis for epileptogenicity of penicillin. To verify that recurrent inhibition is functionally decreased in the penicillin epileptic focus and to assess alternative sites for penicillin action, this phenomenon was investigated at the cellular level. Neurons were recorded extracellularly and response to stimuli monitored throughout the transition from normal cortex to epileptogenic cortex. Stimuli employed were peduncular stimulation (to test recurrent inhibitory pathways), epicortical stimulation (to test inhibitory pathways, bypassing the recurrent collateral system), and forepaw footpad shock (to test the responsiveness ofneurons to afferent input). In normal cortex, PT cells were inhibited by peduncular or epicortical stimulation and excited by forepaw stimulation, with the excitation followed by a period of inhibition. In the penicillin focus, inhibition was not observed in response to any of the 3 stimuli, and the excitatory response to forepaw stimulation was maintained. The bursting non-PT cells, most likely candidates for interneurons, exhibited excitation in response to peduncular and epicortical stimulation, consistent with involvement in inhibitory pathways. Nonetheless, in the penicillin focus, excitatory response to peduncular and epicortical stimulation was maintained. Excitatory response to forepaw stimulation was also maintained in the penicillin focus. The results demonstrate a loss of effectiveness of recurrent inhibition measured at the PT cell body in the penicillin focus. Further, the reduction in inhibitory feedback occurs in conjunction with maintained or enhanced excitability of the neurons which are most likely candidates for inhibitory interneurons. Thus, penicillin is most likely exerting its effect at the inhibitory synapses onto PT cells in the cortex, thereby allowing excitatory input to have greater influence on neuronal firing.

The effects of denervation and stimulation upon synaptic ultrastructure.

Quantitative studies of synaptic ultrastructure were made in the upper layers of cat cerebral cortex. Tissues were from intact cortex and from long-term (chronic) undercut cortex with or without electrical stimulation. The synaptic effects of chronic electrical stimulation of denervated cortex are most readily understood as growth and remodeling of synaptic elements. Associated with chronic stimulation were increases in: symmetric membrane contacts; areas of round and flat vesicle containing terminals; dendritic shaft contacts; and synaptic contact lengths. Even without stimulation there were indications of synaptic plasticity in denervated cortex; compared with intact cortex, synapses having symmetric membrane contacts showed an increase in bouton area and an increase in synaptic contacts on dendritic shafts. These data are consistent with the observations of others in which axonal terminal growth occurred after differentation. But it appears that chronic electrical stimulation in the adult nervous system promotes significantly more plasticity than occurs without stimulation. In a functional sense stimulation in the present experiments produced effective inhibition which did not occur with denervation alone. Thus the plasticity observed with stimulation had both structural and functional components.