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D J Perkel

Publications and source records attributed to D J Perkel.

26 records · Page 2Linked to original sources
PubMed1990

Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices.

1. The pharmacological and biophysical properties of excitatory synapses in the CA1 region of the hippocampus were studied using patch electrodes and whole-cell recording from thin slices. 2. Excitatory postsynaptic currents (EPSCs) had a fast component whose amplitude was voltage insensitive and a slow component whose amplitude was voltage dependent with a region of negative slope resistance in the range of -70 to -30 mV. 3. The voltage-dependent component was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovalerate (APV; 50 microM), which had no effect on the fast component. Conversely, the fast voltage-insensitive component was abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) which had no effect on the slow component. 4. In Ringer solution with no added Mg2+ the current-voltage relation of the NMDA component was linear over a much larger voltage range than in the presence of 1.3 mM-Mg2+. 5. The NMDA component of the EPSC could be switched off with a hyperpolarizing voltage step at the soma. The kinetics of this switch-off was used to estimate the speed of clamp control of the subsynaptic membrane as well as the electrotonic distance from the soma. The kinetic analysis of the EPSC was restricted to synapses which were judged to be under adequate voltage control. 6. For those synapses that were close to the soma the time constant for decay for the non-NMDA component, which was voltage insensitive, ranged from 4-8 ms. 7. The rise time for the NMDA component was 8-20 ms and the time constant for decay ranged from 60-150 ms. 8. During increased transmitter release with post-tetanic potentiation or application or phorbol esters, both components of the EPSC increased to a similar extent. 9. These experiments provide a detailed description of the dual receptor mechanism operating at hippocampal excitatory synapses. In addition, the experiments provide an electrophysiological method for estimating the electrotonic distance of synaptic inputs.

2-Amino-5-phosphonovalerate↗
PubMed1989

An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation.

The phenomenon of long-term potentiation (LTP), a long lasting increase in the strength of synaptic transmission which is due to brief, repetitive activation of excitatory afferent fibres, is one of the most striking examples of synaptic plasticity in the mammalian brain. In the CA1 region of the hippocampus, the induction of LTP requires activation of NMDA (N-methyl-D-aspartate) receptors by synaptically released glutamate with concomitant postsynaptic membrane depolarization. This relieves the voltage-dependent magnesium block of the NMDA-receptor ion channel, allowing calcium to flow into the dendritic spine. Although calcium has been shown to be a necessary trigger for LTP (refs 11, 12), little is known about the immediate biochemical processes that are activated by calcium and are responsible for LTP. The most attractive candidates have been calcium/calmodulin-dependent protein kinase II (CaM-KII) (refs 13-16), protein kinase C (refs 17-19), and the calcium-dependent protease, calpain. Extracellular application of protein kinase inhibitors to the hippocampal slice preparation blocks the induction of LTP (refs 21-23) but it is unclear whether this is due to a pre- and/or postsynaptic action. We have found that intracellular injection into CA1 pyramidal cells of the protein kinase inhibitor H-7, or of the calmodulin antagonist calmidazolium, blocks LTP. Furthermore, LTP is blocked by the injection of synthetic peptides that are potent calmodulin antagonists and inhibit CaM-KII auto- and substrate phosphorylation. These findings demonstrate that in the postsynaptic cell both activation of calmodulin and kinase activity are required for the generation of LTP, and focus further attention on the potential role of CaM-KII in LTP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

Topography of the afferent connectivity of area 17 in the macaque monkey: a double-labelling study.

The various structures afferent to area 17 (or V1) of the macaque monkey have widely differing retinotopic organizations. It is likely that these differences are reflected in the topographic organizations of the projections from these structures to area V1. We have investigated this issue by placing side-by-side injections of two retrograde fluorescent tracers, fast blue and diamidino yellow, in V1. By examining the extent of mixing of the two populations of singly labelled cells and the presence of doubly labelled cells, in different structures, we have characterized the topography of each projection in terms of the size of its axonal arborization and the amount of convergence and divergence. The afferents from the lateral geniculate nucleus (LGN) and from the pulvinar are organized in a point-to-point fashion. The maximum extent of axonal arborization of these afferents is 0.5 mm and these projections demonstrate little scatter (i.e., neighboring LGN neurons project to adjacent regions of V1). The other two subcortical structures examined, the claustrum and the intralaminar nuclei, demonstrate a much larger scatter and wider axonal arborizations in their projections to V1 than do the LGN and pulvinar. Two-dimensional reconstructions were made of the distribution of labelled neurons in extrastriate cortical areas. Using the separation between patches of labelled cells and transitions in myelin-stained sections, we have identified seven separate cortical regions containing labelled cells. Two of these can be identified as area V2 and the middle temporal visual area (MT). Three other regions correspond to areas V3, V3A and V4t. Finally, two more regions of labelling have been distinguished that belong to area V4. These results demonstrate that, at least within the central 6 degrees of visual field, all the presently known extrastriate visual cortical areas project to V1. This result is interesting in view of the fact that only a few extrastriate cortical areas are reported to receive afferents from V1. Three groups of cortical areas can be distinguished on the basis of the characteristics of their cortical connections to V1. The first group contains area V2, V3, and the posterior region of V4. These areas project to V1 with infra- as well as supragranular layer neurons and show limited axonal arborization and scatter in the projection. The second group consists of two regions of labelling in the superior temporal sulcus corresponding to V4t and MT and another on the annectant gyrus (V3A). These regions contain almost exclusively infragranular labelling and show wide axonal arborization and scatter in their projections to V1.(ABSTRACT TRUNCATED AT 400 WORDS)

Amidines↗
PubMed1985

Dendritic spines: role of active membrane in modulating synaptic efficacy.

Dendritic spines have been increasingly implicated as sites for neuronal plasticity. Earlier-theoretical studies of dendritic-spine function have assumed passive membrane, and have consequently predicted that postsynaptic potentials in the dendrite are attenuated when the synapse is located on the spine head rather than on the dendritic shaft. Our studies show that active membrane in the spine head (e.g. voltage-dependent Na+ or Ca2+ channels) can produce amplification rather than attenuation of the postsynaptic potential. The presence and amount of amplification depend on the density of active channels and on the spine-neck resistance. For a given type of spine head, there is an optimal spine-neck resistance; a given change in neck resistance can therefore either increase or decrease the amplitude of postsynaptic potentials. These results support the idea that spines mediate synaptic plasticity and suggest a variety of modulatory mechanisms.

Calcium↗
PubMed1984

Effects of strabismus and monocular deprivation on the eye preference of neurons in the visual claustrum of the cat.

Visual response properties of neurons in the dorsocaudal claustrum were studied in two cats reared with convergent strabismus and three cats reared with monocular lid-suture. In the normal claustrum, most cells respond about equally well to stimulation of either eye (Sherk and LeVay, '81). In the strabismic animals, there was a partial breakdown of binocularity: most cells remained binocular but were influenced more strongly by one eye (usually the contralateral eye) than the other. The loss of binocularity was less extreme in the claustrum than in area 17 of the same animals. In the monocularly deprived cats, claustral cells responded exclusively to the experienced eye. We interpret the changes observed in the claustrum as reflecting changes in the ocular dominance of cortical inputs to the claustrum, rather than as evidence for plasticity within the claustrum itself. Autoradiography was used to study the return projection from claustrum to cortex in monocular deprivation. The cortical labeling pattern resembled that seen in normal cats. To examine whether this return projection might be involved in reducing cortical responsiveness to the deprived eye, recordings were made from area 17 of a monocularly deprived cat before and after ablation of the ipsilateral claustrum by injection of kainic acid. Following ablation, there was no unmasking of cortical responses to the deprived eye. Thus the cortico-claustral loop does not appear to suppress cortical responses to the deprived eye.

Animals↗