The proposed research tests the hypothesis that learning to discriminate between vibratory stimuli will produce synaptic plasticity in the somatosensory cortex of rats and that this plasticity will critically depend on the cholinergic modulation of NMDA channels. In the first experiment, rats will be trained to lick a spout for sugar-water in response to the presentation of one of two different vibratory stimuli applied to an individual whisker. While the rat is learning this discrimination, electrophysiological recordings will be made from single neurons within the vibrissae representation of the somatosensory cortex. The evolution in the responsiveness of those neurons to the training stimuli will be monitored and will subsequently be related to discrimination performance. It is hypothesized that the response of somatosensory cortical neurons to the reinforced stimulus will become enhanced and the response to the nonreinforced stimulus to become suppressed during discrimination learning. In the second experiment, prior to discrimination training and single unit recording, rats will receive systemic injections of the cholinergic agonist BIBN-99 or the antagonist atropine. It is hypothesized that cholinergic facilitation will enhance learning-induced changes in somatosensory cortical neurons and improve acquisition in the discrimination task; conversely, it is hypothesized that cholinergic suppression will block learning-induced synaptic plasticity and impair acquisition in the discrimination task. In the third experiment, prior to discrimination training and single unit recording, rats will receive systemic injections of the NMDA antagonist MK-801. It is hypothesized that NMDA receptor blockade, like cholinergic suppression, will prevent the emergence of learning-induced synaptic plasticity and will impair acquisition in the discrimination task. Results from these experiments will provide unique evidence directly linking the cholinergic system to memory formation and synaptic plasticity, and in turn will help to illuminate the relationship between memory loss and cholinergic hypofunction in Alzheimer's disease.
| Garcia, A Denise R; Han, Young-Goo; Triplett, Jason W et al. (2018) The Elegance of Sonic Hedgehog: Emerging Novel Functions for a Classic Morphogen. J Neurosci 38:9338-9345 |
