All ETDs from UAB

Advisory Committee Chair

John Hablitz

Advisory Committee Members

Lynn Dobrunz

Kevin Kirk

Lori McMahon-Wakefield

Lucas Pozzo-Miller

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


The actions of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) are tightly regulated to ensure effective information processing as well as prevention of excess excitatory activity, which can lead to seizures and neurological disorders such as epilepsy. Drugs which enhance the effects of GABA are used as anesthetics, sedatives and anticonvulsants. Using whole-cell patch clamp recordings from neocortical neurons, we examined the mechanisms of GABAergic modulation that occur when kainate receptors (KARs) are activated. First, we address a novel signaling mechanism for the KAR-mediated facilitation of GABAergic synaptic transmission. Our first observation involved the presence of presynaptic KARs located on the presynaptic terminals of interneurons. These presynaptic KARs are homomeric and calcium permeable. Upon activation of KARs, inositol trisphosphate (IP3) receptors are activated which causes calcium release from intracellular stores. This calcium influx is believed to be involved in the increase in vesicular release or facilitation observed upon bath application of kainate (KA) to slices from prefrontal cortex (PFC). Second, we identify the specific subunit involved in the observed KAR mediated facilitation. It is known that homomeric glutamate receptor (GluR)5 as well as homomeric GluR6 subunit containing KARs can be calcium permeable. Using GluR6 knockout mice, we determined that the GluR6 subunit is not required for KAR mediated facilitation in the PFC. Third, we used the styryl dye FM1-43 to estimate synaptic vesicle recycling iv within presynaptic boutons which synapse onto cortical pyramidal cells. Our observations with FM1-43 support the presence of presynaptic KARs on inhibitory nerve terminals contacting layer II/III pyramidal cells in the PFC. In addition, our results showed a differential modulation by KARs depending on the frequency of afferent activity. Finally, the fourth part of this dissertation involved study of presynaptic KARs modulation using natural stimulation patterns (NSPs). Knowing that KARs differentially modulate vesicular release depending on the frequency of afferent stimulation, we were curious whether the inter-event interval may have an effect on the rates of vesicular release. We observed an increase in vesicular release in the presence of the NSPs and an additional increase in vesicular release in the presence of KA. This suggests that presynaptic KARs differentially modulate vesicular release. In summary, these studies show that presynaptic GluR5 receptors facilitate GABA release in rat PFC and provide new information about underlying signaling mechanisms.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.