Memory encoding and storage in cortical circuits: electrophysiological studies

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Memory traces are thought to consist of networks of simultaneously activated neurons, and new networks can be formed through long-lasting increases (or decreases) in the strength of synaptic connections. Parahippocampal cortical regions, including the entorhinal and perirhinal cortex, process sensory and associational information during the encoding of memory. Research in my lab focusses on how modulatory neurotransmitters and hormones (acetylcholine, serotonin, dopamine, and estrogens) can modulate synaptic communication and neuronal excitability within the entorhinal cortex. Modulatory transmitters play a critical role in memory formation because they powerfully affect both the ongoing processing of sensory information, and the induction of long-lasting changes in synaptic strength. In experiments in the awake rat, changes in the strength of synaptic connections are monitored by recording synaptic responses that are evoked by brief electrical stimulation of synaptic inputs. Recordings from individual neurons in brain-slices are also used to investigate the cellular mechanisms that mediate changes in synaptic connections. The first major line of research investigates effects of neuromodulators on synaptic inputs to the entorhinal cortex, and interactions between multiple input pathways. Heterosynaptic interactions between inputs from the piriform and perirhinal cortex will be investigated to characterize the cellular basis of multi-modal sensory integration. The entorhinal cortex receives strong input from the parasubiculum, and we will determine how serotonin affects synaptic responses and excitability in parasubicular neurons, and how this impacts the entorhinal cortex. Estrogens promote cognitive function and enhance excitatory synaptic transmission in the entorhinal cortex, and we will now determine the estrogen receptors involved, and examine effects of estrogen on inhibitory and cholinergic synaptic transmission. The second major line of research focusses specifically on changes in entorhinal circuitry induced by the transmitter dopamine which may promote responses to stimuli associated with motivation and reward. Conditioned cues associated with reward activate dopamine neurons, and we will determine how these cues affect synaptic responses and cell firing in entorhinal neurons. We will also determine the role of dopamine in controlling the induction of lasting increases and decreases in synaptic strength. Optogenetic stimulation techniques will be used to determine how tonic and phasic synaptic release of dopamine affects excitatory transmission and the excitability of entorhinal neurons. This program of research will determine fundamental neuronal mechanisms through which neuromodulators regulate the circuitry of the entorhinal cortex, to promote sensory processing and mnemonic function.