| Description |
Temporal features of sound are important in acoustic communication, including speech recognition in humans. Neurons selective for acoustic elements such as duration of sound and interval between successive sound pulses were discovered in the anuran central auditory system; however, the underlying mechanisms remain unclear. To investigate these mechanisms, we combined in vivo whole-cell patch recordings from midbrain neurons and focal pharmacological manipulations. Further, to identify how integration of synaptic inputs contributes to the temporal selectivity of midbrain neurons, we developed an algorithm to estimate the stimulus-related changes in excitatory and inhibitory conductances over time. In Chapter 1, we show that selectivity for short-duration sounds results from integration of short-latency, sustained inhibition with delayed, phasic excitation; active membrane properties appeared to amplify responses to effective stimuli. Blocking GABAA receptors attenuated stimulus-related inhibition, revealed suprathreshold excitation at all stimulus durations, and decreased short-pass selectivity without altering resting potentials. Pharmacological attenuation of excitation confirmed that inhibition tracks stimulus duration and revealed no evidence of postinhibitory rebound depolarization inherent in coincidence models of duration selectivity. These results strongly support an anticoincidence mechanism of short-duration selectivity, wherein inhibition and suprathreshold excitation show greatest temporal overlap for long duration stimuli. In Chapter 2, we examined the mechanisms that underlie long-interval selectivity. Neurons selective to long intervals between pulses showed a broad spectrum of selectivity hinting at the presence of multiple mechanisms. In all long-interval selective cases, excitation showed a rate-dependent decrease; in most cases, even slow rates elicited depression of excitatory conductance. Inhibition was ubiquitous in these neurons and had diverse time courses across cells. The relative amplitude of inhibition to excitation correlated significantly with long-interval selectivity. Pharmacological attenuation of inhibition decreased selectivity in some cells but, across neurons, primarily increased response gain. These findings demonstrate that long-interval selectivity is mechanistically diverse and force a re-evaluation of current models for long-pass interval selectivity. In Chapter 3, we derive the mathematical equations used to estimate changes in excitatory and inhibitory conductances. We show that Izhikevich's hybrid model estimates conductances more accurately than a passive single-compartmental model; this was achieved by tuning conductance constants to filter out near-threshold voltage-dependent currents. |
