Cortical pathways and local circuits mediating memory formation: electrophysiological studies.

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Memory traces are thought to consist of networks of simultaneously activated neurons, and a major mechanism through which new networks can be formed is through long-lasting increases (or decreases) in the strength of synaptic connections between neurons. My research is aimed at understanding how new memory traces are formed through long-lasting changes in the strength of synaptic connections between brain cells. The hippocampal formation and surrounding parahippocampal cortical regions are thought to combine different types of sensory input during the encoding of memory, and the long-term consolidation of memory is thought to involve other parts of the brain including the neocortex. Research in my lab focusses on how the modulatory neurotransmitters acetylcholine and dopamine, that contribute to arousal, can modulate ongoing synaptic processing within the parahippocampal region of the rat and contribute to the induction of long-lasting changes in synaptic strength. I use electrophysiological and pharmacological techniques to investigate the role of these transmitters in the parahippocampal region. In the awake rat, changes in the strength of synaptic connections are assessed by monitoring synaptic field potentials that are evoked by brief electrical stimulation of synaptic inputs. Recordings from single neurons in slices of brain tissue are also used to investigate the cellular mechanisms that mediate changes in synaptic connections. The first major line of research is aimed at understanding how the entorhinal cortex (an important parahippocampal area) processes and encodes sensory input. There are three series of studies in this line of research. The first builds upon our finding that release of acetylcholine causes a suppression of synaptic strength in piriform (olfactory) cortex inputs to the entorhinal cortex, and will use brain-slice recordings to determine the cellular mechanisms of this suppression. A second series of studies will examine the cellular basis of multi-modal sensory integration in the entorhinal cortex by characterizing interactions between synaptic inputs from the piriform and perirhinal cortex. The third series of studies will focus on how inputs to the entorhinal cortex from the parasubicular division of the hippocampal formation are modulated by acetylcholine. The parasubiculum contributes to spatial processing and we will investigate how acetylcholine induces a “relative facilitation” of synaptic responses during repeated stimulation. Results will contribute to developing theories of the role of this pathway in spatial processing. The second general line of research is concerned with changes in entorhinal circuitry induced by the transmitter dopamine that is thought to promote cognitive processing of stimuli associated with motivation and reward. We will investigate how dopamine release associated with anticipation of food-reward, or rewarding electrical stimulation of the hypothalamus, leads to changes in the strength of synaptic inputs to the entorhinal cortex. High concentrations of dopamine suppress synaptic inputs, and low concentrations facilitate synaptic strength, and experiments will determine the intracellular signals that mediate these effects. Additional experiments will determine how dopamine can gate the induction of lasting increases or decreases in synaptic strength. “Optogenetic” stimulation techniques will also be used to determine the effects of synaptic release of dopamine on glutamatergic transmission and firing behaviour of entorhinal neurons. This line of research will help characterize how sensory processing and mnemonic function may be altered in the entorhinal cortex by dopamine, and will also clarify the fundamental neuronal mechanisms that mediate these changes.