Overview
We study how local circuits in the cerebral cortex encode and transform sensory information. We use the rodent auditory cortex as a model system to investigate how cellular and network properties shape cortical responses to a continuous and temporally complex stream of sensory data. Research in the Wehr lab combines aspects of both cellular, systems, and computational neuroscience, by using the tools of molecular biology and cellular physiology to address systems-level questions. By using a variety of electrophysiological approaches, in particular in vivo whole cell recording methods in combination with molecular manipulations, we are trying to identify the cellular and synaptic mechanisms with which cortical circuits process auditory information, leading ultimately to our perceptual experiences of acoustic streams, such as music and speech.
Projects
Synaptic mechanisms of sound processing in awake rats.
Silencing of activity in genetically specified cell types.
Disruption of balanced excitation and inhibition after hearing loss.
Level dependence of contextual modulation in auditory cortex.
Synaptic mechanisms of sound processing in awake rats.
How does synaptic processing in auditory cortex transform the neural representation of temporally structured sounds such as music and speech? Auditory cortical neurons can show distinct neural codes in awake animals that aren’t seen under anesthesia, such as sustained firing responses to long sounds, and rate-coded responses to temporally structured sounds. We are investigating the synaptic processing underlying these responses by recording from auditory cortical neurons in unanesthetized rats, using in vivo whole-cell methods.
Silencing of activity in genetically specified cell types.
Most systems neuroscience is correlative. In order to establish causal relationships between neuronal activity, cortical function, and behavior, we must be able to manipulate the activity of specific types of neurons. In collaboration with the Kentros lab and the Neill lab, we are using new optogenetic and pharmocogenetic techniques to silence neurons under the control of cell-type specific promoters. With these silencing tools we will be able to investigate the contributions of different interneuron types to different functional forms of synaptic inhibition in auditory cortical function. By combining optogenetics with new tools for imaging neuronal activity and tracing cortical microcircuitry, we can record from and manipulate connected neurons, allowing us to explore cortical circuits in unprecedented detail.
Disruption of balanced excitation and inhibition after hearing loss.
Hearing loss disrupts the receptive fields of cortical neurons, but the synaptic mechanisms underlying these changes remain unknown. We used in vivo whole cell recordings to demonstrate that changes in the balance of excitation and inhibition play a key role. These mechanisms may be involved in the generation the phantom ringing in the ears known as tinnitus. More details on this project can be found in Scholl & Wehr 2008.Level dependence of contextual modulation in auditory cortex.
Responses of cortical neurons to sensory stimuli within their receptive fields can be profoundly altered by the stimulus context. In visual and somatosensory cortex, contextual interactions have been shown to change sign from facilitation to suppression depending on stimulus strength. We discovered that in auditory cortex, in contrast, contextual interactions were primarily suppressive across all probe levels. This suggests that context has fundamentally different effects in auditory cortex than it does in visual or somatosensory cortex. More details on this project can be found in Scholl, Gao & Wehr 2008.
Autistic individuals have a range of perceptual processing deficits, including a striking hypersensitivity to auditory stimuli. A disruption in the balance of excitation and inhibition in cortical circuits has been proposed as a model for autism and autism spectrum disorders. We are testing this hypothesis in transgenic mice generated by our collaborators Jennifer Hoy and Phil Washbourne.
