Carolyn R. Houser, Ph.D.

Work Address:
CHS
Los Angeles, CA 90095 CHS
Los Angeles, CA 90095

Affiliations
Affiliations
Professor, Neurobiology
Member, Brain Research Institute, Neuroscience GPB Home Area
Research Interests
Much of the work in our laboratory is focused on identifying morphological changes that may contribute to the development of epilepsy. In epilepsy, neurons in some specific regions of the brain, such as the hippocampus, become hyperexcitable and begin to be activated or fire in synchrony, thus producing spontaneous seizures or epilepsy. One of the major causes of epilepsy appears to be damage to the brain through severe, prolonged seizures or head trauma early in life. It then requires some time for spontaneous seizures to develop. Our goal is to identify the anatomical and neurochemical changes that occur between the initial insult and the subsequent development of epilepsy. Our broad hypothesis is that progressive changes in the GABA system, a major neurotransmitter system that normally helps inhibit or control excessive neuronal activity in the brain, are critical for the development of epilepsy. By studying brain tissue from animal models of epilepsy and human tissue from patients with temporal lobe epilepsy, we have identified several interesting changes that could contribute to the development of seizure activity. We are pursuing these findings through immunohistochemical and biochemical studies of the hippocampus. First, some but not all neurons that use GABA as their neurotransmitter are damaged in epilepsy. We are attempting to determine why some GABA neurons are easily damaged while others are spared. Since some GABA neurons remain, we are studying the changes that occur in these neurons to determine if there is reorganization of their axons and synapses with other neurons. Finally, we are studying changes in the receptors through which GABA influences the activity of other neurons. Recently, in a mouse model of temporal lobe epilepsy, we have found that some specific subunits of GABA-A receptors are altered in ways that could contribute to seizure activity. More detailed knowledge of such changes could lead to the development of new pharmacological methods for treating existing epilepsy, and, ultimately, preventing the development of this disorder.
Biography

Research Interest: Neurochemical anatomy, neuronal plasticity and development of the CNS

The broad research interests of the laboratory are the neurochemical anatomy and morphological plasticity of the mammalian central nervous system. Research is focused on the gamma-aminobutyric acid (GABA) system. GABA is an extremely important neurotransmitter in many brain regions and may also have trophic roles during development of the nervous system. Both the presynaptic neurons that use GABA as a neurotransmitter and the postsynaptic sites at which these neurons exert their influence are being studied. Immunohistochemical and in situ hybridization methods are used to study the localization and regulation of the proteins and mRNAs of two forms of the synthesizing enzyme for GABA, glutamic acid decarboxylase (GAD) and multiple subtypes of the GABA-A receptor. Interrelationships between the GABA neurons and their receptors are being studied in the normal brain, during development and in experimental conditions in which the GABA system is altered. The brain region of major interest in these studies is the hippocampus.

The goals of a second but related group of studies are to identify the morphological and neurochemical changes that occur in epilepsy. Such changes are being studied in human tissue and in animal models of seizures. These models allow us to identify the changes that occur following an initial insult to the nervous system and then to determine the progression of morphological and neurochemical changes that may lead to the development of increased excitability and spontaneous seizures.

Publications
Error in include template "/web/fdb5/www/gpb/institution/publications": can't read "allow_redirect_p": no such variable