Joshua X. Gittelman, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): The broad objective of this research is to understand how neural filters are formed, i.e. how do neurons respond to certain stimuli, but not to others? Many auditory filters are believed to be formed in the inferior colliculus (1C), including the response selectivity for the direction of frequency modulation (FM), where a cell may respond strongly to the preferred direction of FM, but not to the non-preferred FM. In the past, most studies on FM direction selectivity used extracellular electrodes to record spikes, and then used the spike counts to infer the mechanisms underlying FM direction selectivity, including patterns of synaptic input and the cell's intrinsic properties. I will use the whole-cell patch-clamp technique to directly measure sound- evoked post-synaptic potentials (PSPs) and spikes, as well as basic biophysical properties such as input resistance and cell capacitance. I will also use the PSP data to calculate the timing and magnitudes of the sound-evoked synaptic conductances, including separate values for inhibition and excitation. These direct measurements will enable me to evaluate the mechanisms underlying FM direction selectivity in the 1C in a more comprehensive manner than possible with extracellular electrodes. There are three major goals. First, I will characterize intracellularly the extent to which 1C neurons are selective for the direction of FM, including the rate and intensity of the FMs. Second, I will determine whether and to what extent FM direction selectivity is created de novo in the 1C, or is inherited from the synaptic inputs, where the afferent neurons are themselves directionally selective. This will include an analysis of the extent to which direction selectivity is created by spectral-temporal asymmetries of excitation and/ or inhibition. Finally, I will compare the direction selectivity that is present in the PSPs to the direction selectivity in the spike counts to determine whether and to what extent spike threshold enhances direction selectivity. The major treatments for hearing loss include cochlear implants and hearing aids. Any circuit that distinguishes biologically relevant sounds from background noise could benefit both treatments. Because FMs are an important component of speech, understanding how mammalian brains process FMs may help to improve the degree to which hearing aids and cochlear implants can distinguish speech sounds in noisy environments. [unreadable] [unreadable] [unreadable] [unreadable]