Parvalbumin neurons enhance temporal coding and reduce cortical noise in complex auditory scenes

Abstract

Cortical representations supporting many cognitive abilities emerge from underlying circuits comprised of several different cell types. However, cell type-specific contributions to rate and timing-based cortical coding are not well-understood. Here, we investigated the role of parvalbumin neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli which are highly dynamic in time and compete with stimuli at other spatial locations. Parvalbumin neurons play a fundamental role in balancing excitation and inhibition in cortex and sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based coding, and the robustness of temporal representations to spatial competition, has not been investigated. Here, we address these questions in auditory cortex of mice using a cocktail party-like paradigm, integrating electrophysiology, optogenetic manipulations, and a family of spike-distance metrics, to dissect parvalbumin neurons’ contributions towards rate and timing-based coding. We find that suppressing parvalbumin neurons degrades cortical discrimination of dynamic sounds in a cocktail party-like setting via changes in rapid temporal modulations in rate and spike timing, and over a wide range of time-scales. Our findings suggest that parvalbumin neurons play a critical role in enhancing cortical temporal coding and reducing cortical noise, thereby improving representations of dynamic stimuli in complex scenes.

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction

“…Additional Network Noise: An increase in network-level noise in response to suppression of PV cells has been directly demonstrated by multiple groups (5,79,80). After using our model to demonstrate PV cell hypoactivity in the male KI network, the basal network noise (3-4 Hz) delivered to PYR2 exclusively was increased by a factor of 1.5x (76).…”

“…After using our model to demonstrate PV cell hypoactivity in the male KI network, the basal network noise (3-4 Hz) delivered to PYR2 exclusively was increased by a factor of 1.5x (76). This increase in mean firing rate of PYR2 -representing an increase in network-noise in response to PV cell hypoactivity -has been used in previous models (76) and was set in order to match in vivo experimentally-derived changes in basal firing rates in response to PV suppression (5).…”

“…Cortical parvalbumin (PV)-positive fast-spiking cells are a distinct class of inhibitory neurons characterized by their expression of the Ca 2+ -binding protein, PV (1)(2)(3). Their unique biophysical properties allow them to drive potent, precise inhibition, effectively controlling the temporal dynamics of the excitatory and inhibitory inputs (4)(5)(6) that support critical brain functions (7)(8)(9). At a network level, PV cells are responsible for generating and regulating gamma oscillations (10), Hz rhythmic fluctuations in brain activity that correlate with cognitive performance (11)(12)(13) and are impaired in anxiety disorders (14), schizophrenia (SCZ) (15,16), and Alzheimer's Disease (AD) (17,18).…”

Spatially resolved molecular and cellular atlas of the mouse brain

“…More importantly, these two clusters of neurons were both Pvalb positive. Pvalb interneurons are widely distributed in the auditory system, which are well-tuned for sound frequency 74 and could enhance temporal coding in the auditory pathway 75 . The distinct distribution of excitatory Pvalb and inhibitory Pvalb neurons in different auditory nuclei, suggesting that two subtypes of Pvalb neurons play different roles in processing sound information.…”

Syngap1regulates the synaptic drive and membrane excitability of Parvalbumin-positive interneurons in mouse auditory cortex

“…By providing fast inhibition onto postsynaptic PC cell somata and proximal dendrites, PV+ cells exert fine control on their output (Moore and Wehr, 2013; Tremblay et al, 2016), while SST+ cells targeting apical dendrites of postsynaptic PCs exert specific control over dendritic synaptic integration (Kawaguchi and Kubota, 1997; Chiu et al, 2013). In recent years, novel transgenic and optogenetic technologies have allowed for precise labeling and manipulation of these two major classes of GABAergic interneurons in vivo in order to address their specific role in auditory processing and sound perception (Letzkus et al, 2011; Pi et al, 2013; Hamilton et al, 2013; Keller et al, 2018; Ceballo et al, 2019; Chai et al, 2022; Nocon et al, 2023). Specifically, SST+ neurons have a dominant role in the integration of information across multiple auditory frequencies and respond relatively slowly to a narrower range of tones (Lakunina et al, 2020; Li et al, 2015).…”