The development of new technologies for manipulating brain function by gene targeting in mice has far outstripped the available behavioral methods for functional assessments. The current proposal will address three specific aims to develop additional behavioral models that are suitable for testing cognitive functions in genetically altered mice. Particular attention is given in the selection of these assessments to the need for time/cost efficient procedures that are, in addition, well grounded in both behavioral theory and studies of neural systems. One assessment of memory using retention for exposure to novel olfactory/gustatory information is intended to provide a highly efficient screen for medial temporal lobe function. The proposed studies include parametric examination of the properties of this model and test for its dependence on circuitry and neural mechanisms critical for other behavioral assessments that are less efficient to implement, such as models for spatial memory. In a second specific aim appetitive Pavlovian conditioning will be used to sequentially assess first-order conditioned responses, second order conditioning and the effects on behavior of devaluing the unconditioned stimulus. These tests provide analysis of motivational/incentive learning tied to specific neural systems. In the third specific aim we will develop a protocol for examining repeated acquisition of learning using new information in each test session. As a model, this olfactory guided learning task can be exploited to examine brain function concurrently with behavioral learning. Similar to the outline of studies for the first memory model, for each subsequent model proposed studies include parametric examination of the properties of the model and tests for its dependence on circuitry and neural mechanisms critical for the behavioral assessment. The models will be developed using F1 hybrids of C57B/6 129svImJ mice and comparisons with the inbred parent strains will also be made.
| Lee, Hey-Kyoung; Takamiya, Kogo; Han, Jung-Soo et al. (2003) Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell 112:631-43 |
