REGULATION OF NEURONAL EXCITABILITY IN THE AMYGDALA
The goal of the research in this laboratory is to provide the basic knowledge that is necessary for the development of effective therapeutic strategies aimed at preventing or treating certain neurological and psychiatric disorders where dysfunction of the amygdala plays a pivotal, causative role.
Mechanisms regulating neuronal excitability in the amygdala, and the alterations in these mechanisms in anxiety disorders. As the GABAergic and glutamatergic system are the primary determinants of neuronal excitability in the brain, we are using electrophysiological techniques (whole-cell patch-clamp, intracellular and field potential recordings), as well as molecular methods, to study the modulation of GABAergic and glutamatergic synaptic transmission in the amygdala of normal and fear-conditioned rats and mice. We also study plasticity of glutamatergic synaptic transmission (Long-Term Potentiation, LTP) in these animals, as LTP is considered to be the cellular mechanism for acquiring and consolidating information, and therefore alterations in synaptic plasticity can have a profound effect on the function of a brain region.
UNDERSTANDING THE ROLE OF THE AMYGDALA IN EPILEPTOGENESIS
Epileptogenesis is the process whereby, after an acute brain insult, such as traumatic brain injury, progressive pathophysiological alterations in neuronal networks occur that lead to the development of epilepsy. We recently identified an important mechanism regulating neuronal excitability and epileptic activity in BLA. We demonstrated that, in the rat BLA, kainate receptors containing the GluR5 subunit (GluR5KRs) regulate GABAergic inhibitory synaptic transmission via both postsynaptic and presynaptic mechanisms. The relevance of these findings to epilepsy is suggested by additional findings that a) activation of GluR5KRs can induce epileptiform activity in in vitro amygdala slices, and epilepsy in vivo, b) expression of these receptors is elevated in epileptic temporal lobe regions, in both humans and rats, c) GluR5-KRs are a primary target of a commonly used antiepileptic drug (topiramate), and d) GluR5-KR antagonists prevent limbic seizures. Our work is progressing to identify the alterations in GABAergic and glutamatergic synaptic transmission in the BLA, during the course of epileptogenesis, and determining whether changes in the function of GluR5KRs contribute to these alterations. We are investigating whether genetic elimination or pharmacological blockade of GluR5KRs can inhibit epileptogenesis. Unraveling the role of GluR5KRs in the pathogenesis of epilepsy may have significant implications for the discovery of antiepileptogenic drugs that have fewer side effects, as GluR5KR antagonist do not affect normal synaptic transmission and GluR5KRs are not widely distributed in the brain.
Dr. Maria Braga Bio
USU Office of Research