Joyce A. Duncan

Morphological changes in pyramidal cells of mammalian neocortex associated with increased use

Abstract After long-term electrical stimulation of the brain, which presumably produced increased neuronal use, histological studies were made of neocortical neurons involved in transcallosal and extracallosal systems. Adult cats with implanted electrodes received 20 trains (2 sec each) of electrical stimulation to the suprasylvian gyrus daily for several weeks. In four cats, brain stimulation was paired with foreleg shock (trained), in two, it was not (untrained). Cortical tissues ipsilateral and contralateral to the stimulated side were prepared with a modified Golgi-Cox method. In cortex contralateral to the stimulated side, apical dendrites of layers II and III pyramidal cells had significantly more branchings in terminal regions, greater lengths, and terminated nearer the pia than they did on the stimulated side. There were also more spines on oblique, vertical, and terminal portions of apical dendrites. Increases in oblique and vertical spine counts appeared to be more related to training than to just brain stimulation. Qualitatively, apical dendritic terminals in contralateral cortex had fine branchings, filamentous bare twigs, especially long spines, convolutions with close packing of spines, acute angles of terminals reflecting from the pia, and a general appearance of increased density of apical dendrites near the pia. The observed changes in neuronal structure described in these experiments are interpreted as evidence that increased use of specific pathways to the cerebral cortex produces postsynaptic growth in some cortical neurons.

A STUDY OF PYRAMIDAL CELL AXON COLLATERALS IN INTACT AND PARTIALLY ISOLATED ADULT CEREBRAL CORTEX

Abstract A quantitative study was made of pyramidal cell axon collaterals in Golgi impregnated adult cat cerebral cortex. Cellular samples were obtained from 3 groups, intact, undercut and long-term electrically stimulated undercut cortex. Undercut tissue had cells with significantly fewer axon collaterals and fewer branches than did intact. Long-term electrically stimulated undercut tissue contained neurons which were not different from intact in these two measures. There was, therefore, a preservation of axonal morphology in stimulated undercut, adult cortex. Results do not support a theory of axonal proliferation to explain supersensitivity in partially isolated mature cortex. The preservation of axonal components and the preservation of dendritic spines, previously reported, indicates the prevention of some degenerative changes in certain cortical neurons brought about by long-term electrical stimulation.

Prevention of supersensitivity in partially isolated cerebral cortex

Abstract 1. 1. A portion of the marginal gyrus of the cerebral cortex on each of fifteen cats was undercut 3–4 mm deep. In terminal experiments under chloralose, 2–18 weeks later, local electrical stimulation produced after-discharges (in 12 cats) which had a longer duration on the undercut side than on the intact side. 2. 2. Another group of seventeen cats, each with an undercut marginal gyrus, received daily electrical stimulation (subthreshold for after-discharges) of the undercut cortex starting 1 week after undercutting (6 weeks delay in two cats). Total stimulation was about 400 applications at 0.6 mA, 400 at 0.8 mA and 200 at 1.0. mA. In terminal experiments under chloralose 1 week after the end of stimulation (6 weeks for one cat), fourteen of these cats did not show supersensitivity of the undercut cortex. 3. 3. These results suggest that chronic electrical stimulation can prevent the development of supersensitivity.

Long-term status of pyramidal cell axon collaterals and apical dendritic spines in denervated cortex

Abstract Cortices of animals in 3 groups were denervated by undercutting at 4 or 40 days of age or at adulthood. Months later electrocortical seizures were studied in terminal experiments and cortical tissues prepared for light microscopic study. Four measures, assumed to be descriptive of or related to axon collateral proliferation, were made: number of axon collaterals, length of collaterals, number of collateral branches and number of apical dendritic spines. Data from adult intact cortex served as controls. Increases in number of collaterals and collateral length were observed, the best evidence being in the 40-day animals. However, since collateral branching decreased, the data do not support the concept of proliferation as described in young brains. If dendritic spines are valid indicators of synaptic contacts then the observed significant loss of spines argues against the maintenance of functional connections, if indeed they were established, following denervation at any age. There were no obvious relationships between morphological changes and duration of afterdischarges. A persistent alteration was frequently seen in cortex which had been undercut at 4 days of age. Lower lying pyramidal cell axons bifurcated with nonrecurrent spread parallel to the glia infiltrated site of the old fiber paths. This glial barrier appeared to have prevented centripetal axon growth.

Acetylcholinesterase activity in partially isolated cerebral cortex after prolonged intermittent stimulation.

Abstract Acetylcholinesterase (AChE) levels were determined in control samples of cat cerebral cortex, in partially neuronally isolated (undercut) cortex, and in undercut or intact cortex that had received long-term intermittent electrical stimulation. Assay of AChE activity was based on an automatic titration method using methalcholine as substrate. Tissues from ten of 15 undercut cerebral cortices showed the expected decrease in AChE. Long-term intermittent electrical stimulation of undercut cortex prevented the expected decrease in AChE in seven of 12 cortices. Previous data showed that similar long-term stimulation could prevent some electrical manifestations of supersensitivity. The present findings implicate, in part, a cholinergic system in the phenomenon of cortical supersensitivity.