PubMed Health⌕ Search

Biomedical subjects

K S Wilcox

Publications and source records attributed to K S Wilcox.

8 recordsLinked to original sources
PubMed1994

Properties of inhibitory and excitatory synapses between hippocampal neurons in very low density cultures.

The whole cell patch clamp technique was used to examine the electrophysiological properties of embryonic hippocampal neurons maintained in a very low density (VLD) culture preparation. The goal of these experiments was to establish the viability of the VLD culture as a model system in which to study regulation of neurotransmission at single monosynaptic connections, in the absence of polysynaptic innervation. Depolarization of neurons in the VLD culture revealed voltage-dependent sodium, calcium, and potassium currents which were blocked with, respectively, tetrodotoxin (TTX), cobalt, and tetraethylammonium and 4-aminopyridine. When pairs of neurons were simultaneously recorded, action potentials evoked in presynaptic neurons elicited either excitatory or inhibitory postsynaptic currents (EPSCs or IPSCs, respectively). The dual component EPSCs were due to the activation of both types of postsynaptic, ionotropic glutamate receptors: N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Evoked IPSCs were due to the activation of postsynaptic gamma-aminobutyric acid (GABA) receptors. Both excitatory and inhibitory synapses exhibited short term depression in response to high frequency stimulation, although IPSCs were routinely decreased to a much greater degree than EPSCs. Spontaneous miniature EPSCs and IPSCs were found to persist in TTX, were blocked by the same pharmacological antagonists which blocked evoked responses, increased in frequency in response to hypersomotic solution, and were unaffected by changes in extracellular calcium concentration. mIPSCS were found to occur at a significantly lower frequency than mEPSCs. These experiments indicated that neurotransmission in the VLD cultures occurs in a manner consistent with the quantal hypothesis and, therefore, the VLD culture is a good model for studying excitatory and inhibitory neurotransmission between isolated pairs of neurons. In addition, these experiments, performed under comparable physiological conditions, demonstrated that there are fundamental differences underlying neurotransmitter release between excitatory and inhibitory neurons.

Animals↗
PubMed1994

Paired pulse depression in cultured hippocampal neurons is due to a presynaptic mechanism independent of GABAB autoreceptor activation.

Most rapid synaptic inhibition in the vertebrate forebrain is mediated by GABA acting via GABAA and GABAB postsynaptic receptors. GABAergic neurotransmission exhibits frequency-dependent modulation; sequential inhibitory post-synaptic currents (IPSCs) evoked with interstimulus intervals between 25 msec and 4 sec routinely result in the attenuation of the amplitude of the second IPSC. This form of synaptic plasticity is known as paired pulse depression (PPD). The mechanism of PPD is presently unknown and the experiments performed in this study were designed to determine directly the location of the mechanism of PPD in hippocampal neurons maintained in low-density tissue culture. Evoked IPSCs were recorded between pairs of cultured neurons grown in relative isolation that were simultaneously being recorded with the whole-cell, patch-clamp technique. It was therefore possible to measure miniature IPSCs (mIPSCs) originating from the same synapses that were being stimulated to evoke release. PPD occurred routinely in this system, but the amplitudes of mIPSCs following IPSCs were unchanged. These results indicate that a presynaptic mechanism mediates PPD. The inability of GABAB receptor antagonists to block PPD revealed that this form of presynaptic plasticity was not due to autoinhibition of transmitter release via activation of presynaptic GABAB receptors. However, manipulations that significantly lowered the probability of release of neurotransmitter during the first action potential of a trial (e.g., lower calcium or baclofen) prevented the development of PPD. These results indicate that, under baseline conditions, the quantal content for IPSCs is relatively large for a single action potential, but the quantal content rapidly decreases, such that subsequent action potentials consistently result in much smaller IPSCs for periods as long as 4 sec.

Animals↗
PubMed1989

In vitro electrophysiology of neurons in the lateral dorsal tegmental nucleus.

The lateral dorsal tegmental nucleus (LDT) provides ascending cholinergic projections to forebrain structures such as prefrontal cortex, septum, habenula, and thalamus, but relatively little is known of the physiology of LDT neurons. Intracellular recordings from LDT neurons in guinea pig brain slices found that most neurons fired action potentials either tonically or in bursts. The voltage dependent characteristics of the neurons suggest that a prolonged afterhyperpolarization due to an outward potassium current and a low-threshold calcium conductance contributed to these two modes of firing. Intracellular injections of Lucifer Yellow and subsequent staining for NADPH-diaphorase activity permitted positive identification of cholinergic neurons.

Action Potentials↗
PubMed1988

Electrophysiological properties of neurons in the lateral habenula nucleus: an in vitro study.

1. The electroresponsive characteristics of neurons in the lateral habenula were studied with intracellular recordings in a brain slice preparation of guinea pig diencephalon maintained in vitro. One hundred and two neurons met the criteria for recording stability, and of these, 18 were analyzed in detail. For these 18 neurons, the mean resting membrane potential was -61.9 mV, the mean input resistance was 124 M omega, and the mean spike amplitude of fast action potentials was 60.3 mV. 2. Lateral habenula neurons were found to have distinct patterns of activity dependent on membrane potential. At membrane potentials more positive than -65 mV, depolarization elicited trains of sodium-dependent fast action potentials. At membrane potentials more negative than -65 mV, slight depolarization elicited a tetrodotoxin-insensitive wave of depolarization, called a low-threshold spike (LTS), from which a burst of fast action potentials were triggered. The principal conductance underlying the LTS is a low-threshold calcium conductance, which is inactivated at membrane potential more positive than -65 mV and deinactivated when the membrane is hyperpolarized to potentials more negative than -65 V. 3. Upon termination of injected hyperpolarizing current, many neurons displayed oscillation in membrane potential at a frequency of 3-10 Hz, thereby generating repetitive bursts of fast spikes. 4. The pattern of neuronal activity in lateral habenula neurons was highly sensitive to slight alterations in membrane potential. The ability of these neurons to fire action potentials in two modes, tonically and in bursts, and the propensity of these neurons to dramatically alter their output in response to transient hyperpolarizing input, indicate that transmission through this relay in the dorsal diencephalic conduction system may be greatly augmented by relatively small hyperpolarizing influences on the individual neurons.

Action Potentials↗
PubMed1986

Kainate and electrolytic lesions of the lateral habenula: effect on avoidance responses.

Male Sprague Dawley rats (n = 24), which received either bilateral electrolytic lesions, kainic acid lesions or sham treatments in the lateral habenula, were tested for acquisition of a one-way, conditioned avoidance response. Animals with electrolytic lesions failed to learn the avoidance task within 15 trials. In contrast, rats with kainic acid lesions performed as well as the control group. The results indicate that the disruption of the septal-medial habenula-interpenduncular nucleus pathway may be responsible for the observed avoidance deficit in electrolytically lesioned animals.

Animals↗
PubMed1986

Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat.

Neurons in the lateral habenula (LHb) of rats have efferent projections that terminate in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA), where cell bodies of dopamine-containing neurons are located. In order to study the influence of the habenula on dopaminergic activity, single-cell electrophysiological techniques were used to record unit discharge of dopamine-containing neurons in the SNC and VTA during electrical stimulation of the LHb or adjacent structures. Dopamine-containing neurons in the SNC and VTA were identified by their characteristic spike duration (greater than 2 msec), discharge rate (2-8 spikes/sec), and irregular firing pattern. Analysis of peristimulus time histograms showed that 85% of SNC cells and 91% of VTA neurons were inhibited after single pulse stimulation (0.25 mA, 0.1 msec) of the LHb. The mean time between stimulation and onset of inhibition was 11 msec (range, 2-22 msec) and mean duration of maximal suppression was 76 msec (range, 20-250 msec). Stimulation of structures adjacent to the LHb (hippocampus, lateral thalamus, medial dorsal thalamus, medial habenula) had little or no effect. Destruction of the fasciculus retroflexus, the fiber pathway that contains most habenular efferents, blocked the stimulation effects on dopamine-containing neurons. Destruction of the stria medullaris, which contains most habenular afferents, did not alter the inhibitory effect of habenular stimulation. Injection of a cytotoxin, kainic acid, in the LHb 1 week before recording sessions blocked the inhibitory consequences of habenular stimulation. These experiments show that activation of neuronal perikarya in the LHb causes orthodromic inhibition of dopamine-containing neurons in SNC and VTA via the fasciculus retroflexus.

Animals↗