Mammalian perception is a dynamic process. Animals and humans can exist in a variety of environments, and can optimize performance for distinct sensory tasks. This perceptual adaptability is believed to depend on the flexibility of neocortical circuits, and specifically on the sensory tuning of excitatory neurons. Several theories have proposed that diversity in the sensory tuning of inhibitory interneurons (IN) is key to neocortical dynamics. In support of this idea, in vitro studies have distinguished 2 IN classes by their responses to excitatory input. One IN type is sensitive, responding robustly to weak initial stimuli and subsequently adapting if a high-frequency stimulus is maintained. This IN type typically demonstrates fast- spiking action potentials and parvalbumin expressing. A second type of IN is initially insensitive, but subsequently facilitates if stimuli persist. This type is typically regular-spiking and somatostatin expressing. Despite the theoretical importance of this prediction, and in vitro support for it, these IN types have not been distinguished in vivo. We will test the hypothesis that different IN types show distinct sensitivity to the strength of sensory stimuli, and distinct dynamic adjustments to sustained high-frequency input. We will test this hypothesis by measuring IN receptive fields in layers II/III of the vibrissa barrel cortex with 3 complementary techniques: Extracellular recording, intracellular recording, and 2-photon imaging. Tetrode recording will provide a high neural yield, and allow distinction between regular- and fast-spiking neurons. Intracellular recording will provide conclusive cell type identification and unique access to subthreshold responses. 2-photon imaging will provide direct visualization of IN sub-types in mice with fluorescently labeled neurons, and the ability to track their activation using calcium imaging. We will test this hypothesis by parametric variation of the velocity and frequency of vibrissa motion, and with increasingly naturalistic stimuli, including whisking in air and across a surface. Accessibility of active sensing (whisking) in a preparation amenable to stable recording is a key advantage of this system. The barrel cortex has distinct benefits for testing our hypothesis. Barrel cortex is a high-resolution sensory area in a rodent, where unique techniques (e.g., imaging fluorescently labeled IN) are possible. Further, our laboratory has substantial expertise in this system. Testing IN receptive fields follows directly from our prior studies, and from our working theory of sensory-driven neocortical dynamics. These IN are hypothesized to contribute not only to normal function, but also to disease. For example, maladaptive changes in parvalbumin staining IN are predicted to be causal in schizophrenia. While systematic probes of IN function are more complicated in higher areas, sensory input to primary areas is an ideal initial preparation to test this hypothesis, and should provide insight into IN function across cortical areas.

Public Health Relevance

These studies have direct relevance to understanding basic mechanisms underlying human mental illness. The key hypothesis tested is that distinct types of neocortical interneurons have distinct functions in the in vivo cortex. Maladaptive changes in the exact types we will examine are thought to be causal in Epilepsy and Schizophrenia: Understanding their potentially crucial role in information processing should have direct implications for interpretation of deficits in these maladies, and may potentially suggest avenues for remediation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Gnadt, James W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brown University
Schools of Medicine
United States
Zip Code
Shin, Hyeyoung; Law, Robert; Tsutsui, Shawn et al. (2017) The rate of transient beta frequency events predicts behavior across tasks and species. Elife 6:
Pritchett, Dominique L; Siegle, Joshua H; Deister, Christopher A et al. (2015) For things needing your attention: the role of neocortical gamma in sensory perception. Curr Opin Neurobiol 31:254-63
Sacchet, Matthew D; LaPlante, Roan A; Wan, Qian et al. (2015) Attention drives synchronization of alpha and beta rhythms between right inferior frontal and primary sensory neocortex. J Neurosci 35:2074-82
Siegle, Joshua H; Pritchett, Dominique L; Moore, Christopher I (2014) Gamma-range synchronization of fast-spiking interneurons can enhance detection of tactile stimuli. Nat Neurosci 17:1371-9
Voigts, Jakob; Siegle, Joshua H; Pritchett, Dominique L et al. (2013) The flexDrive: an ultra-light implant for optical control and highly parallel chronic recording of neuronal ensembles in freely moving mice. Front Syst Neurosci 7:8
Kahn, I; Knoblich, U; Desai, M et al. (2013) Optogenetic drive of neocortical pyramidal neurons generates fMRI signals that are correlated with spiking activity. Brain Res 1511:33-45
Kerr, Catherine E; Sacchet, Matthew D; Lazar, Sara W et al. (2013) Mindfulness starts with the body: somatosensory attention and top-down modulation of cortical alpha rhythms in mindfulness meditation. Front Hum Neurosci 7:12
Normand, Elizabeth A; Crandall, Shane R; Thorn, Catherine A et al. (2013) Temporal and mosaic Tsc1 deletion in the developing thalamus disrupts thalamocortical circuitry, neural function, and behavior. Neuron 78:895-909
Wan, Qian; Kerr, Catherine; Pritchett, Dominique et al. (2011) Dynamics of dynamics within a single data acquisition session: variation in neocortical alpha oscillations in human MEG. PLoS One 6:e24941
Halassa, Michael M; Siegle, Joshua H; Ritt, Jason T et al. (2011) Selective optical drive of thalamic reticular nucleus generates thalamic bursts and cortical spindles. Nat Neurosci 14:1118-20

Showing the most recent 10 out of 20 publications