Optogenetic Silencing of Parvalbumin-expressing Interneurons in Mouse Auditory Cortex: Mechanisms of Gain Modulationology (Neurobiology)

Presenter: Alexandra K. Hartman, Biology (Neurobiology)

Mammalian sensory systems detect relevant stimuli with remarkable sensitivity. This holds true in both high-and low-contrast sensory environments—that is, both when the signal an organism is trying to isolate (say, a pure tone or a visual object) is the strongest signal detected, or is detected in the context of irrelevant signals of equal intensity. The firing rate (‘output’) of a typical auditory neuron increases with stimulus intensity (‘input’). The rate-intensity function is not fixed: gain adjustments—an increase or decrease in response magnitude, relative to baseline—depend on the context in which the stimulus is presented. Contextual gain modulation is thought to be regulated by synaptic input from inhibitory interneurons, but little is known about the connection patterns and cell types that enable it. We use optogenetic tools to address this. Archaerhodopsin is a proton pump activated by yellow-green light. When illuminated, these pumps generate dramatic outward currents that hyperpolarize —or ‘silence’—the neurons in which they are expressed. We will obtain in-vivo recordings from single units in the auditory cortex of anesthetized transgenic mice, in which Archaerhodopsin is expressed in conjunction with Parvalbumin, a protein specific to cortical GABAergic interneurons. The shift in the rate-intensity function of pyramidal cells—before and after Parvalbumin interneurons are dropped from the network—will reveal the physical target(s) of synaptic inhibition.