PubMed Health⌕ Search

Biomedical subjects

W D Knowles

Publications and source records attributed to W D Knowles.

24 records · Page 2Linked to original sources

Electrotonic and dye coupling in hippocampal CA1 pyramidal cells in vitro.

The presence of electrotonic and dye coupling in region CA1 of the guinea-pig hippocampus was investigated in the in vitro hippocampal slice preparation. No electronic coupling potentials were observed in simultaneous recordings from 101 pairs of pyramidal cells. Also, no electrotonically-coupled short latency depolarizations were observed in more than 75 pyramidal cells in response to antidromic activation of the pyramidal cell population, either in normal bathing medium or in medium with lowered Ca2+ concentration and added Mn2+. When the fluorescent dye Lucifer Yellow was injected into pyramidal cell somas, spread of the dye to other cells (dye coupling) was often observed. Injection of Lucifer Yellow into the dendrites of these neurons resulted in many fewer cases of dye coupling. The failure to find electrophysiological evidence of electrotonic coupling among CA1 pyramidal cells suggests that such coupling is not a functionally important feature of this area of the CNS. The lack of electrophysiological evidence of coupling combined with the observation that the site of Lucifer Yellow injection influences the extent of dye coupling further suggests that at least part of the observed dye coupling may be artifactual. Electrotonic coupling may exist in a small percentage of hippocampal pyramidal cells. However, it is not clear that this small amount of coupling is either necessary or sufficient for the synchronization of neural activity as has been hypothesized to occur during epileptogenesis.

Animals↗

Axonal ramifications of hippocampal Ca1 pyramidal cells.

Intracellular injections of Lucifer Yellow into CA1 pyramidal cells of the in vitro guinea pig hippocampal slice enabled us to examine in detail the morphology of the axons of these neurons. We also recorded the electrophysiological responses of these neurons to alvear stimulation. In our morphological examinations, we found that many axons bifurcate in the alveus, with the major branch projecting caudally toward the subiculum and the second, thinner branch projecting rostrally toward the fimbria. Either axons may bifurcate further to produce several axon branches which follow parallel paths in the alveus. These axons also have local collaterals which project into strata oriens and pyramidale. In addition, a very fine plexus of axonal processes was observed in stratum oriens located largely within the basal dendritic field of the parent cell. Our electrophysiological experiments demonstrated that neurons could be activated antidromically by stimulation of the alveus at sites both rostral ad caudal to the neuron. Weak alvear stimulation occasionally evoked small potentials which appeared similar to fast prepotentials. The local axonal ramifications may be involved in recurrent pathways mediating feedback inhibition and/or excitation. The axonal bifurcations also may provide a basis for understanding the origins of fast prepotentials elicited with antidromic stimulation.

Action Potentials↗

Local circuit synaptic interactions in hippocampal brain slices.

The hypothesis that recurrent inhibition in the hippocampus is mediated by interneurons was tested with simultaneous intracellular recordings from the CA1 region of guinea pig hippocampal slices in vitro. In recordings from 101 pairs of pyramidal cells, no interactions were detected in 87% of the pairs. In 13% of the pyramidal cell pairs, spike trains induced in one cell caused inhibitor postsynaptic potentials (IPSPs) in the second cell. No excitatory interactions were detected. In recordings from 43 pairs of cells, where one cell was a pyramidal cell and the other cell was an interneuron, no interactions were detected in 53% of the pairs. In 30% of the interneuron-pyramidal cell pairs, spike trains elicited from the interneuron caused IPSPs in the pyramidal cell. In 28% of the pairs, spike trains elicited from the pyramidal cell caused excitatory postsynaptic potentials (EPSPs) in the interneurons. In 4% of these pairs, reciprocal interactions were seen, with the pyramidal cell exciting the interneuron and the interneuron inhibiting the pyramidal cell. These results support the hypothesis that inhibitory mediate recurrent inhibition in the hippocampus. However, the data also suggest that the interneurons from which these results were recorded were a subset of inhibitory interneurons distinct from the classical basket cell. These interneurons may mediate both feed-forward and recurrent inhibition in the hippocampus.

Action Potentials↗

Differences of in vitro electrophysiology of hippocampal neurons from epileptic patients with mesiotemporal sclerosis versus structural lesions.

In vitro electrophysiologic studies of animal hippocampal slice models of epilepsy have generated hypotheses regarding cellular pathophysiologies associated with epileptogenesis. We tested some of these hypotheses using in vitro intracellular recordings of hippocampal neurons from patients with intractable temporal lobe epilepsy. We compared the electrophysiology of hippocampal neurons from 14 patients with mesiotemporal sclerosis with hippocampal neurons from 7 epileptic patients with structural lesions near the hippocampal biopsy. Both spontaneous and stimulus-evoked synaptic function and action potential firing patterns were observed. Presumed pyramidal neurons from sclerotic hippocampus were significantly less likely to display stimulus-evoked inhibitory postsynaptic potentials (IPSPs) and were more likely to fire spontaneously in bursts of action potentials than were hippocampal neurons from patients with structural lesions. No significant differences were detected in spontaneous postsynaptic potentials, spontaneous rhythmic synaptic events, spontaneous or anode break action potentials, stimulus-evoked excitatory postsynaptic potentials, or stimulus-evoked action potential bursts. Cellular membrane parameters were similar in the two groups, including resting membrane potential, action potential amplitude, action potential half-width, action potential threshold, input resistance, time constant, input/output relationship, and afterhyperpolarization amplitude.

Action Potentials↗