Tag: Michael Wehr

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

Presenter: Alexandra K. Hartman, Biology (Neurobiology)

Poster: B-4

Mentor: Michael Wehr, Institute of Neuroscience

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.

Reopening Auditory Critical Periods by Digesting Perineuronal Nets

Presenter(s): Brynna Paros

Faculty Mentor(s): Michael Wehr & Jonathan Saunders

Poster 64

Session: Sciences

Long-term memories are thought to be encoded by synapses, but synaptic proteins recycle within days. Roger Tsien hypothesized that Perineuronal Nets (PNNs) could provide a durable “punch card” for memory storage. PNNs are tightly-regulated protein lattices surrounding some neurons that inhibit new, while maintaining existing synapses. Understanding speech requires learning the low-level acoustic features of a language, which becomes difficult or impossible after a developmental sensitive period. Do PNNs preserve the acoustic features learned during infancy and inhibit learning new sound categories? Our preliminary experiments demonstrated that the enzymatic digestion of PNNs in auditory cortex enabled mice to learn a distinction between english phonemes (/b/ and /g/) that they were previously unable to. We will present these and other pilot data investigating the effect of PNN digestion on the rate of phonetic acquisition. If PNNs serve as a scaffolding to preserve learned low-level sensory representations, they would be an entirely unexplored therapeutic target for children or elderly people with sensory processing impairments, as well as provide a promising new explanation for the mechanistic origin of developmentally sensitive or critical periods.