Henry G. Wagner

Receptive Field Organization of the S-Potential

The receptive fields of S-potentials have been studied in carp retinas. The relationship between the stimulus intensity and area of stimulation was examined for each component of three different types of S-potential. It appears that for each component there is full summation over a large portion of the retina, a type of organization different from that found in the ganglion cell.

Functional Basis for “On”-Center and “Off”-Center Receptive Fields in the Retina*†

The ganglion cells in the goldfish retina may have either “on”-center or “off”-center receptive fields. Evidence is presented to show that for any cell: (1) Under suitable conditions either pure “on” or pure “off” responses can be evoked by small spot stimuli at any point within the receptive field. (2) The sensitivities of both “on” and “off” processes are maximal in the center of the field. (3) The relative sensitivity of these processes is not constant but changes as a function of position in the field. (4) The response evoked by a stimulus of any size and at any location within the receptive field represents the sum of the contributions from both the “on” and “off” processes.

Effect of acute electrode placement on regional CBF in the gerbil: a comparison of blood flow measured by hydrogen clearance, [3H]nicotine, and [14C]iodoantipyrine techniques.

Regional cerebral blood flow (rCBF) was compared in the gerbil by means of [3H]nicotine, [14C]-iodoantipyrine, and hydrogen clearance techniques. In agreement with other studies, nicotine and iodoantipyrine methods gave virtually identical results. With these methods, it was observed that a reduction in blood flow occurred shortly after insertion of an electrode into the striatum for hydrogen clearance measurement, affecting rCBF throughout the impaled hemisphere. The reduction was moderate (30%) in the striatum and hippocampus, but much greater (70%) in cortical regions. Identical deficits were observed following brief penetrations involving only cortex. Following chronic electrode placement in the striatum, regional blood flow values obtained with [3H]nicotine returned to the control range within 6 h. Blood flow estimates obtained in the striatum with the implanted electrode increased with a similar time course, so that by 6–24 h, hydrogen clearance gave values indistinguishable from control values obtained with [3H]nicotine. These results clearly demonstrate that reduction of CBF subsequent to electrode placement can account for the low values frequently obtained with the hydrogen clearance method in small animals. The distribution of the deficit and the time course of its recovery are similar to blood flow changes associated with spreading depression. While mechanisms responsible for this effect remain to be fully identified, chronic implantation is a practical solution that allows the continued use of hydrogen clearance as a convenient method for repeated measurement of blood flow in the same animal.

Responses to directional stimuli in retinal preganglionic units

1. Extracellular recordings were made from directionally selective ganglion cell units in the isolated frog retina and decapitated Necturus preparation.

Microphysiology of Selectively Vulnerable Neurons

Publisher Summary This chapter describes the changes of neuronal function and other physiological parameters. A common carotid artery (CCA) occlusion in Mongolian gerbils, as well as regional differences of these parameters is also described. In a method described in the chapter, bilateral CCA occlusion produces severe ischemia in both cortex and hippocampus. During CCA occlusion, the forebrain reveals severe ischemia followed by heterogeneous hyperemia after the occlusion is released. The chapter presents the morphological observations that reveal that five minutes of forebrain ischemia in gerbils lead to highly reproducible delayed destruction of neurons in the hippocampal CA1 subfield. With respect to CAlN, notable changes are observed first at two days following ischemia, at the time neurons show some loss of Nissl substance, a more accentuated staining of dendrites, and appearance of clear clefts in the cytoplasm. After three days, most of the CAlN shows severe ischemic injury, followed by neuronal disintegration at four days. The cortex showed no pathological changes during the whole observation period. The described changes of various parameters resulting from five minutes ischemia in gerbils demonstrate that ischemic death of CAlN takes place during the recirculation period.

Role of Circulatory disturbances in the development of post-ischemic brain edema

Two post-ischemic circulatory disturbances that play a significant role in pathophysiology of an ischemic lesion are: (1) reactive hyperemia or hyperperfusion and (2) hypoperfusion. The reactive hyperemia promptly follows release of major cerebral artery occlusion, and it is associated with the opening of the blood-brain barrier to serum proteins and ensuing edema. Prevention or reduction of reactive hyperemia results in significant amelioration of edema and the resulting ischemic brain tissue injury. The post-ischemic hypoperfusion, studied in gerbils, develops soon after recirculation and usually lasts up to 6 h. Its relationship to post-ischemic edema is evident in repeated ischemic insults. In these studies, three ischemic insults of 5 min duration when applied at 1 h intervals, i.e., during the period of hypoperfusion, resulted in a cumulative effect, post-ischemic edema and tissue injury becoming considerably more pronounced that those following a single 15 min ischemia. There was no cumulative effect when the ischemic insults were spaced 3 min or longer than 6 h apart. These observations indicate that repeated ischemic insults taking place during the phase of post-ischemic hypoperfusion may significantly increase the development of edema and brain tissue injury.

Reduced latency of the visual evoked cortical response following cryogenic injury to the cerebral cortex--a neuroexcitatory phenomenon.

Changes in the latency of visual cortical evoked responses (VER) were studied in rats subjected to cryogenic injury of the cerebral cortex. Four hours after cold injury the animals revealed a significant reduction of VER latency, which lasted approximately one week, with maximal reduction in latency occurring after 3 days. A potential role of excitotoxic amino acids in this phenomenon was tested by direct application of glutamate to the exposed cerebral cortex of the control rat and by administration of MK-801, antagonist of the NMDA receptor, in rats subjected previously to cryogenic injury and displaying a significant reduction in the VER latency. The direct application of glutamate to the cortex resulted in a decrease of the VER latency similar in magnitude to that observed after cold injury and this effect could repeatedly be demonstrated after washing out the initial application of the glutamate. The administration of MK-801 in animals subjected previously to cryogenic injury produced, within 5 minutes, reversion of reduced VER latencies. The maximal prolongation of latency occurred 30 min after MK-801 administration and reached in some cases latency values greater than in controls. Reduced latencies, corresponding to those observed originally, reappeared within 2 to 4 hours. Our studies suggest that the described reductions in the VER latencies are related to cortical areas of hyperexcitation due to excessive release of neuroexcitatory transmitters.

Decreased visual evoked cortical response latency associated with cerebral ischaemia in the gerbil

The observation of Xu et al. concerning reduction in latency of the visual evoked responses (VER) following cortical cryogenic injury, prompted us to ascertain whether similar VER changes could be demonstrable after ischaemic brain injury, especially, since both conditions have in common involvement of neuroexcitatory mechanisms. In our study, the Mongolian gerbils, which were subjected to 10 min bilateral carotid occlusion ischaemia, revealed decreased latency of the VER, with the peak of latency reduction between 4 and 7 h. An almost immediate decrease in VER latency was observed when glutamate was directly applied to the pial surface of the brain. These observations indicate that the reduction of VER latency may be related to neuroexcitation induced by release of excitatory amino acids, the latter constituting a widespread phenomenon, concomitant with brain injuries of various aetiologies.

Reduced Latency of Visually Evoked Potentials Following Cortical Injury Indicates Secondary Glutamatergic Neuronal Excitation

While searching for physiological evidence of secondary hyperexcitability following brain injury (Saito et al., 1990), we observed that the latency of visually evoked responses (VER)s was reduced following a unilateral cold lesion to the parietal cortex in the rat. The reduction of latency is interpreted as evidence of a hyperexcitability developing in the visual pathway following cortex injury. Many considerations suggest that glutamate plays an important role in delayed tissue changes following traumatic brain injuries through actions mediated by NMDA receptors (Choi, 1990). We thought this reduction of VER latency may be also of neuroexcitatory nature. This premise was tested by injection of MK-801, a noncompetitive inhibitor of NMDA receptors, in rats when the latency of the VER was reduced following a brain injury.

Observations on cerebral ischaemia in cats at injury threshold levels

The potential for recovery of brain tissue subjected to ischaemia at a threshold level of injury was evaluated in cats subjected to 20 min middle cerebral artery occlusion. In addition to assessment of regional cerebral blood flow and water content, the permeability of the bloodbrain barrier and morphological changes detected by light microscopy were studied at various time intervals. Our observations revealed that although a similar reduction of blood flow during arterial occlusion was found both in the caudate nucleus and the cerebral cortex, the reactive hyperaemia was consistently higher in the caudate nucleus than in the cortex. After 24 h the caudate nucleus also revealed a significantly higher water content and increased vascular permeability than the cortex. Morphological observations at 24 h in areas affected by ischaemia showed widespread, marked ischaemic neuronal injury, whereas at 3 d there was, in addition, a vigorous proliferative reaction of vascular elements. Cats sacrificed at 14 d revealed a remarkably good preservation of neurons, both in the caudate nucleus and cortex which otherwise showed a few circumscribed, small, infarcts surrounded by normal nerve cells. Our study suggests that neurons injured at threshold level have a considerable capacity for recovery. Otherwise, with a similar degree of ischaemia, the caudate nucleus appears more prone to increased vascular permeability and oedema than the cerebral cortex.