Neural analogs of habituation in the mammalian brain will be studied with neurophysiological techniques. The rat in vitro hippocampal slice, a preparation from a brain structure implicated in learning and memory functions, will be employed. Set I: studies will determine whether habituation occurs in the monosynaptic temporo-ammonic pathway (TA-CA1). Classical characteristics of habituation will be assessed from recordings of extracellular fiber volley, population EPSP and population spike field potentials and will be compared to features of habituation in the perforant to dentate pathway (PP-Dentate). Functional and anatomic differences in these pathways may be reflected in habituation parameters. These data will provide a framework for intracellular studies (II and III). Set II: will determine whether the postsynaptic cell contributes to habituation in TA-CA1 and PP-dentate pathways. First, habituation will be characterized in intracellular studies of pyramidal and granule cells of TA-CA1 and PP-dentate pathways. Four membrane events accompanying synaptically activated habituation will be evaluated: resting membrane potential; input resistance; membrane time constant; and threshold to spiking. Second, current- and voltage-clamp techniques will be employed to manipulate postsynaptic activity independently of afferent input during the course of habituation. Set III: studies will determine modulatory effects of habituation in the TA-CA1 and Schaffer/Commissural (SCP) network. Modulation of activity in the network as a function of habituation of TA-CA1 will be studied with single pulse, paired pulse, and LTP paradigms activated by stimulation of SCP. These will be the first intracellular studies of habituation in mammalian brain. They will be critical to defining the nature of habituation and establishing possible associational properties. They may also show that habituation is a major candidate synaptic mechanism providing a potentially useful decremental influence on information flow through an adaptive neural network.
