The input/output properties of a neuron are modifiable. Characterizing changes in input/output properties is imperative to understanding how neural activity changes in response to ongoing changes in network activity. While there are several examples of input-driven changes in neural excitability, it is not known how ongoing synaptic activity modulates the input/output properties of a neuron. The long-term goal of the proposed research is characterize how ongoing synaptic input affects the integrative properties of layer V pyramidal neurons in prefrontal cortex (PFC). The first specific aim of this proposal will further test the initial observation that low rates of synaptic stimulation produce changes in the excitability of pyramidal neurons in layer V of PFC. These experiments will identify the conductances and neurotransmitter receptors involved in the observed changes. These experiments involve whole-cell patch clamp recordings from the soma of layer V PFC neurons. The second specific aim will test the hypothesis that the changes occur in the dendrites in a manner that depends on the frequency and site of stimulation. Completion of this aim will provide insight into whether the plasticity is short-term or long-term and whether it is homeostatic or putatively involved in learning. These experiments will involve both whole-cell somatic and dendritic recordings. The third specific aim will test for differences in changes in the properties of two classes of neurons with different repertoires of membrane conductances: those that project within the cortex and those that project subcortically. The overriding hypothesis of this specific aim is that changes in input/output properties depend on the specific membrane conductances available to be modified.
Understanding how ongoing synaptic input affects the input/output properties of a neuron could have implications for treatment strategies for a variety of disorders associated with changes in neural excitability including epilepsy. In addition, the prefrontal cortex is involved in several cognitive processes such as action planning and working memory. Thus, characterizing changes in prefrontal neurons is vital for developing treatment strategies for a host of neurological disorders associated with deficits in these cognitive processes, including: Alzheimer's disease, attention disorders such as ADHD, autism, and schizophrenia.
|Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H (2015) Cell-Type Specific Channelopathies in the Prefrontal Cortex of the fmr1-/y Mouse Model of Fragile X Syndrome. eNeuro 2:|
|Kalmbach, Brian E; Chitwood, Raymond A; Dembrow, Nikolai C et al. (2013) Dendritic generation of mGluR-mediated slow afterdepolarization in layer 5 neurons of prefrontal cortex. J Neurosci 33:13518-32|