GABAergic inhibition shapes the response properties of nearly every neuron in the auditory cortex, either directly (through synaptic inhibition onto th examined neuron) or indirectly (by inhibiting the excitatory cells that synapse onto it). This inhibition is generated by the roughly 20% of cortical neurons that are GABAergic. These neurons fall into multiple classes with distinct anatomical, chemical, and biophysical specializations, enabling intricate and precise modulation of cortical function. A full account of how the different types of inhibitory neurons shape cortical processing of sounds has yet to be generated, but will require A) that we understand the sensory or behavioral conditions in which each type is activated, and B) that we understand how their activation affects information processing in their direct targets and in the network overall. The goal of this proposal is to testin awake mice whether parvalbumin (PV) and somatostatin (SST) neurons, the two most numerous types of cortical inhibitory neuron, contribute differentially to auditory processing, in the context of two main questions about their function: 1) whether their effect is selective to non primary inputs or is similar across all parts of a neuron's receptive field, and 2) to what extent they mediate the effects of acoustic context on neural responses.
Both normal aging and mild hearing loss are associated with profound changes in processing of temporal and spectral context. The associated difficulties with speech comprehension lead to social isolation and significant decreases in quality of life. This work will allow us to relate low-level changes in intracortical inhibition to the high-level changes in perception and behavior observed in aging and disease, which will guide development of clinically useful manipulations to restore lost auditory processing capabilities.
|Raju, Chandrasekhar S; Spatazza, Julien; Stanco, Amelia et al. (2018) Secretagogin is Expressed by Developing Neocortical GABAergic Neurons in Humans but not Mice and Increases Neurite Arbor Size and Complexity. Cereb Cortex 28:1946-1958|
|Hoglen, Nerissa E G; Larimer, Phillip; Phillips, Elizabeth A K et al. (2018) Amplitude modulation coding in awake mice and squirrel monkeys. J Neurophysiol 119:1753-1766|
|Morrill, Ryan J; Hasenstaub, Andrea R (2018) Visual Information Present in Infragranular Layers of Mouse Auditory Cortex. J Neurosci 38:2854-2862|
|Larimer, Phillip; Spatazza, Julien; Stryker, Michael P et al. (2017) Development and long-term integration of MGE-lineage cortical interneurons in the heterochronic environment. J Neurophysiol 118:131-139|
|Phillips, Elizabeth A K; Schreiner, Christoph E; Hasenstaub, Andrea R (2017) Diverse effects of stimulus history in waking mouse auditory cortex. J Neurophysiol 118:1376-1393|
|Phillips, Elizabeth A K; Schreiner, Christoph E; Hasenstaub, Andrea R (2017) Cortical Interneurons Differentially Regulate the Effects of Acoustic Context. Cell Rep 20:771-778|
|Larimer, Phillip; Spatazza, Julien; Espinosa, Juan Sebastian et al. (2016) Caudal Ganglionic Eminence Precursor Transplants Disperse and Integrate as Lineage-Specific Interneurons but Do Not Induce Cortical Plasticity. Cell Rep 16:1391-1404|
|Phillips, Elizabeth Ak; Hasenstaub, Andrea R (2016) Asymmetric effects of activating and inactivating cortical interneurons. Elife 5:|
|Seybold, Bryan A; Phillips, Elizabeth A K; Schreiner, Christoph E et al. (2015) Inhibitory Actions Unified by Network Integration. Neuron 87:1181-1192|