Abstracts

RATIONALE: [gamma] - Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the mammalian brain. GABA inhibition via interneurons, which synapse on the dendritic trees and soma, can offset neuronal excitation occurring during epileptic seizures. We have demonstrated in previous studies that the inhibitory interneurons can regulate neuronal bursting activity and that the pattern of bursting behavior depends upon the synaptic weight and delay of the inhibitory connection, as well as the location of the synapse. In this study, two types of GABA receptors, GABA[sub]A[/sub] and GABA[sub]B[/sub], are investigated at several locations of the inhibitory synapse using a multicompartmental pyramidal neuron model. We also investigate the role of GABA[sub]A[/sub] and GABA[sub]B[/sub] inhibition in the pattern of bursting activity.
METHODS: We build a multicompartmental pyramidal model of synaptically connected neurons using the simulation software GENESIS. Three simplified pyramidal neurons and an interneuron are modeled in this study: two neurons are synaptically connected with excitatory synapses forming a loop, a neuron where random input is applied to generate action potentials, and an inhibitory interneuron, which synapses on GABA[sub]A[/sub] or GABA[sub]B[/sub] receptors of one of the modeled pyramidal neurons, in a negative feedback loop. We investigate the influences of GABA[sub]A[/sub] and GABA[sub]B[/sub] inhibition on the pattern of bursting activity in model pyramidal neurons. The inhibitory interneurons have inputs on GABA[sub]A[/sub] or GABA[sub]B[/sub] receptors at the soma, main dendrites, or branch dendrites of the modeled pyramidal neurons. The values of median and standard deviation in interspike interval (ISI) analysis are used for examination of bursting patterns.
RESULTS: Simulations show that GABA[sub]B[/sub] inhibition is stronger than GABA[sub]A[/sub] inhibition when inhibitory interneuron synapses on the soma, main dendrites, or branch dendrites of the modeled pyramidal neurons. When the inhibitory interneuron synapses on GABA[sub]A[/sub], rather than GABA[sub]B[/sub], receptors of any locations of the modeled pyramidal neurons larger synaptic weight is needed to block bursting activity. The inhibitory action of GABA[sub]A[/sub] as well as GABA[sub]B[/sub] is stronger when the inhibitory interneuronal synapse is close to the soma. The synaptic weight of the inhibitory interneuron has to be increased in order to prevent bursting activity when the interneuron synapses on a branch dendrite.
CONCLUSIONS: GABA inhibition regulates the bursting behavior in a multicompartmental pyramidal model. GABA[sub]B[/sub] inhibition is stronger than GABA[sub]A[/sub] inhibition on any location of inhibitory synaptic connections in a multicompartmental pyramidal neuron model. Both GABA[sub]A[/sub] and GABA[sub]B[/sub] inhibition are stronger when the inhibitory interneuronal synapse is close to the soma of the modeled pyramidal neurons. The potential for GABA[sub]B[/sub] inhibition to play an important modulatory role is supported by these findings.
[Supported by: NIH grant NS 38958]