Synaptic Plasticity in the Inferior Colliculus

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DESCRIPTION (provided by applicant): Our overall goal is to understand how activity may alter auditory signal processing in the inferior colliculus (IC), a critical auditory center in the midbrain. As the midbrain hub of the auditory pathway, the neurons in the central nucleus of the IC integrate different types of ascending auditory information. The IC also gates the information reaching the auditory cortex through direct excitation and direct inhibition of the medial geniculate body. The unique position of IC has made it a recent target for deep brain stimulation. However, little is known about how evoked activity, either acoustic or electrical, may alter information transmission in IC neurons. Synaptic inputs are critical in shaping the responses of IC neurons to sound. In the central nervous system, it is well known that the synapses may be modified, e.g. potentiated or depressed in an activity dependent manner. Synaptic plasticity may play an important role for learning & memory and the development of neural circuits. Although long term potentiation (LTP) and depression (LTD) exist in the IC, their role is unclear. They might shape the neuronal responses to sound based on recent activity in the auditory pathway in adults. One critical factor in synaptic plasticity is the relative timing between the pre- and post- spike activity. Spike Timing Dependent Plasticity (STDP) is a formal way of evaluating that relationship often inducing both LTP and LTD in the same neuron when a different temporal order is used. Our project will elucidate the character of STDP in the IC. Since both sound processing and STDP phenomena vary temporally in the same millisecond time range, STDP may be highly relevant for the synaptic processing of sound. Moreover, a distinct advantage of using STDP in the experimental study of synaptic plasticity is that the location of the plasticity is clear and is restricted to the pre- and/or post synaptic sites of the recorded neuron in the IC. Our main goal is to investigate how activity may change the sound evoked responses in the inferior colliculus in mice in vivo. For this purpose, we will record sound-evoked neural responses with either juxtacellular/cell-attached or whole cell in vivo recording techniques. We will use STDP to compare the response to sound before and after the neuron is "trained" by combining the sound evoked response with action potentials evoked by single-cell current injection (nano-stimulation). Separate experiments will investigate the effects of STDP on spectral (frequency) tuning to sound, temporal modulation of sound relevant for communication, and responses to binaural stimuli relevant to sound localization. In complementary experiments, we will use a brains slice preparation of IC to investigate whether STDP is the same in different neuron types. Specifically, we will test GABAergic and glutamatergic neurons in GAD67-GFP transgenic mice where GABAergic neurons are labeled. Generally, the IC and lower auditory centers are considered less 'plastic' than auditory cortex. Our project may change this view and reveal physiologically relevant activity-dependent changes in IC. Such knowledge may be essential to understand normal hearing and for therapy, training, rehabilitation after hearing loss.