Ricardo Valenzuela - US grants

[unreadable] DESCRIPTION (provided by applicant): Synapses are specialized junctions between cells in the nervous system that allow for the transmission of information from one neuron to the next. An important property of synapses is that they have the ability to increase and decrease their strength in response to activity and this is known as long- term potentiation (LTP) and long-term depression (LTD) respectively. It is believed that this synaptic plasticity is the cellular basis of memory formation. Recent work using paired whole-cell recordings of neurons in area CAS of the hippocampus has indicated that synapses exist in states where their ability to undergo further plasticity is determined by their previous synaptic changes. Understanding the mechanisms of this newly discovered property is crucial to understanding how synaptic plasticity and thus perception, learning, memory, etc. are mediated and regulated. The state characteristics and mechanisms of silent synapses, synapses that lack AMPA receptors but contain NMDA receptors, are not well understood in the context of the synaptic states model. This study proposes to use paired whole-cell recordings of neurons to: 1) Identify the receptor dependence of synapse unsilencing at the resolution of the connecting between only two cells; 2) Determine whether any difference in the state characteristics of silent synapses and synapses silenced through an depression protocol; 3) Determine the mechanisms underlying the differences between silent, recently silent, and active synapses. Brain cells are connected together by synapses which allows them to form interconnected neural circuits that are responsible for the biological computations that underlie the brain's functions. This research proposes to study the properties and mechanisms that allow synapses to adjust their strength which will give us a greater understanding of learning and memory. [unreadable] [unreadable] [unreadable]