The olfactory system can perform remarkable tasks in the identification and detection of odors. The circuits that perform these tasks and how they are influenced by experience are poorly understood. Our recent work has demonstrated that early prenatal experience results in changes in odor-evoked responses, circuit connectivity and lateral inhibition. Here we propose to analyze experience-dependent circuit-level changes in olfactory bulb lateral inhibition using electrophysiological and optogenetic approaches. Specifically, we will perform experiments and analysis designed to address the following three specific Aims.
Aim 1) To determine if odor conditioning alters the intrinsic properties of olfactory bulb neurons. In many parts of the brain, one consequence of increased excitatory input is reduced excitability of principle neurons. We will test whether the excitability of mitral and/or tufted cells as well as particular interneuron types differs in animals subject to long-term odor exposure.
Aim 2) To determine how odor conditioning changes synaptic properties in olfactory bulb circuits. Our preliminary data indicate that exposure to an M72 ligand increases the strength of lateral inhibition onto tufted, but not mitral cells following activation of the M72 glomerulus. We will evaluate this plasticity by determining the circuit mechanisms of plastic change. Specifically we will determine which synapses or cells are responsible for these enhanced responses.
Aim 3 : To determine how odor conditioning affects odor-evoked responses. Our published and preliminary data show that long term exposure causes a broad increase in mitral cell odor evoked responses (measured by in vivo 2-P calcium imaging in anesthetized animals). In this Aim we propose to expand on this observation by examining odor-evoked responses in tufted cells and specifically in mitral and tufted cells identified as receiving input in glomeruli that respond to the conditioned odor.
We propose to examine the plasticity of brain circuits that are involved in processing of olfactory stimuli. We will test the hypotheses about the circuit mechanisms by which early postnatal experience alters local circuitry within the olfactory bulb of mice and determine the rules that govern these experience-dependent changes, focusing on how specific patterns of activity in genetically defined populations of sensory neurons shape circuits that are involved in lateral inhibition. The olfactory system is a useful model for the analysis of sensory function, plasticity and dysfunction and its function is compromised in a variety of disease states, including neurodegenerative diseases such as Parkinson?s and developmental disorders such as autism.
