Search

Early morphological events associated with the genesis of epileptiform activity are essentially unknown, despite significant progress on morphological correlates of potentially related plastic neural phenomena. Hippocampal area CA1 shows the capacity to generate epileptiform bursting activity after certain patterns of electrical stimulation. Using an in vitro slice kindling preparation, we found increases in the numbers (areal densities) of shaft and sessile spine synapses in hippocampal subfield CA1 within minutes following the establishment of stable afterdischarges. These data strongly suggest that synaptogenesis is associated with the early stages of epilepsy formation.

Astrocytic glia are important for maintaining synaptic function during physiological activity. Recent hypotheses concerning epilepsy suggest a role for astrocytes in the control of neuronal excitability and in pathogenesis. This report provides morphological evidence that the periodic electrical stimulation used in the kindling model of epilepsy induces astrocytic hypertrophy and an increase in shaft synapse density in the CA1 region of the hippocampus. The Schaffer collateral pathway in the stratum radiatum of CA1 of five pairs of rats was kindled in vivo. Control animals received the same number of stimulations at a lower intensity and frequency. The animals were killed 24-48 h after reaching the criterion of five generalized seizures, and the brains were examined by electron microscopy. Kindling produced a 37% and 33% increase in the volume fraction of astrocytic processes in the middle and distal portions, respectively, of the s. radiatum in CA1. In the same tissue, the number (areal density) of shaft synapses was increased 25% in the s. radiatum of animals exhibiting generalized seizures. On the other hand, the areal density of degenerating synapses in both kindled and control animals was low and not significantly different. These results suggest that both synaptogenesis and hypertrophy of astrocytes contribute to an early stage of epileptogenesis when degenerative changes of the sort that might induce gliosis were not prominent in the tissue under study.

A number of experimental approaches have indicated differential interneuronal connectivity following differential experience during both development and adulthood. In Golgi preparations, prolonged maze training was reported to alter dendritic branching of distal apical dendrites of Layer IV and V pyramidal neurons in adult rat occipital cortex. To determine the specificity of this effect to direct involvement in the visual aspects of training, the effects of monocular maze training, using a split-brain procedure and opaque contact occluders, was examined in the present study. Rats were maze trained with unilateral or alternating monocular occlusion, while non-trained rats with unilateral or alternating monocular occlusion were handled briefly and given water reward. There was no within-animal effect of fixed occluder position in non-trained controls. In unilaterally-occluded trained rats, Layer V pyramidal neurons in occipital cortex opposite the open eye had greater oblique dendritic length in the distal region of the apical dendrite than did those opposite the occluded eye. Similarly, rats trained with alternating occlusion had greater distal apical oblique dendritic length in Layer V occipital pyramidal neurons than did non-trained controls. This indicates that morphological sequelae of training are concentrated in areas processing information associated with visual aspects of the training and renders unlikely general metabolic or hormonal causation of such effects.

While recent studies indicate that proposed regulation of visual cortex plasticity by norepinephrine (NE) probably involves 6-hydroxydopamine (6-OHDA) effects other than NE depletion, reports of diminished neuronal maturation and reduced postweaning sensitivity to environmental conditions in animals treated with anti-adrenergic compounds continue to suggest a role for NE in neocortical development. To assess its possible role in development of a highly organized neocortical structure, the effects of postnatal 6-OHDA administration upon development of the somatosensory cortical posteromedial barrel subfield (PMBSF), which subserves the large facial whiskers, were observed in mice with whiskers in the middle row of the face removed unilaterally. Treatment with 6-OHDA caused 96–98% depletion of NE in parietal cortex. There were no effects of (or lesion interactions with) 6-OHDA treatment on barrel size in measures of Nissl-stained neurons, and 6-OHDA effects on numerical measures of dendritic branching of Golgi-impregnated non-pyramidal neurons in PMBSF were negligible. There were, however, effect of 6-OHDA treatment upon the highly ordered arrangement of dendrites within barrels. In 6-OHDA-treated animals, the class I (spiny and sparsely spined) cell dendrites were less attracted to the barrel hollow. In controls, for class I cells with their somata within the barrel wall, there was a high correlation between the distance from the soma to the hollow and the amount of dendrite in the wall, reflecting the distance the dendrite traverses to the hollow. In 6-OHDA-treated animals, this correlation was absent, i.e., cells at any distance from the hollow tended to have a high percentage of dendrite in the wall. For cells in the hollow, in controls, a relatively constant majority of dendrite stayed in the hollow. In 6-OHDA-treated animals, the amount of dendrite that hollow cells extended into the wall increased as the somata became closer to the wall, suggesting a loss of systematic governance of the orientation of dendrites by the overall pattern of the barrel. Thus the effect of 6-OHDA administration was to reduce enforcement of the normal rules of barrel organization. Two other findings related to the spread of dendrites into septa and neighboring barrels. It was found that 6-OHDA treatment increased the frequency of class II cells (smooth cells) having significant amounts of their dendrites extending outside the original barrel. Similarly, the drug treatment increased the number of class I cells extending their dendrites into adjacent denervation-induced barreloids. Given evidence that afferent activity is involved in postnatal organization of the PMBSF, all 3 findings accord with the proposal that the physiological effects of NE are to suppress background activity and to potentiate specific afferent activity, which might attract or selectively retain dendrites growing in regions of highest thalamic afferent density.

This study examined anatomical correlates of: (1) long-term potentiation (LTP); (2) equivalent low frequency synaptic activity; (3) continuous high frequency synaptic activation which did not produce LTP; and (4) synaptic inactivation by high Mg2+/low Ca2+ incubation in hippocampal subfield CA1 in the in vitro slice, and examined the persistence of changes at 10-15 min, 2 h and 8 h after stimulation. After potentiating stimulation (6 trains at 100 Hz for 1 s or 200 Hz for 0.5 s), compared to an equivalent number of low frequency stimuli (1 Hz for 600 s), there were increases in numbers of shaft and sessile spine synapses (synapses on stubby, headless spines). This suggested an increase in the number of shaft synapses onto inhibitory interneurons and/or an enhancement of synapse formation on pyramidal neurons possibly involving initial formation of shaft synapses and a transition from shaft, to sessile spine, to full grown spine synapses. Postsynaptic spine heads also assumed a rounder shape, as indicated by decreases in spine perimeter to area ratios, contact lengths, and the percentage of 'cup' shaped spines. There was no effect of potentiating stimulation on bouton or spine areas. After continuous high frequency synaptic activation (40 Hz or 100 Hz for 10 min), which produced no apparent LTP, there were no changes in synapse numbers or spine head shape parameters. However, in contrast to effects of LTP, there was an increase in bouton mitochondrial area and a marginal increase in bouton area compared to the low frequency condition. Inactivation did not affect any of these measures. LTP-associated increases in numbers of shaft and sessile spine synapses persisted over an 8 h incubation period, while the effect on spine shape disappeared after 2 h. Physiologically-demonstrable LTP persisted over the 8 h period. Effects of continuous high level activation on mitochondrial and bouton areas were even more transient, disappearing 2 h after stimulation. These findings: (1) confirm previously reported effects of potentiating stimulation on synapse numbers and spine shape; (2) indicate that spine shape changes are not necessary for the maintenance of LTP; and (3) indicate that continuous high frequency activation which does not produce potentiation has different and non-persisting effects from potentiating stimulation.

Embryonic cerebral cortex transplanted to the occipito-parietal region of newborn rats makes connections with the host brain. Retrograde labeling studies after injection of HRP into transplants showed input from the contralateral cortex and ipsilateral thalamus of the host. Transplant projections to the host thalamus and striatum have also been identified.