Biology subjects

Krall, R. F.

Publications and source records attributed to Krall, R. F..

3 recordsLinked to original sources

bioRxiv2025

Cell-type-specific plasticity in synaptic, intrinsic, and sound response properties of deep-layer auditory cortical neurons after noise trauma

Peripheral trauma, such as noise-induced hearing loss (NIHL), triggers compensatory plasticity in the auditory cortex (ACtx) to maintain auditory function. While cortical plasticity in superficial cortical layers has been relatively well studied, the plasticity mechanisms governing deep-layer excitatory projection neurons remain less understood. Here, we investigated the plasticity of layer (L)5 extratelencephalic (ETs) and L6 corticothalamic neurons (CTs) following NIHL. Using a combination of in vitro slice electrophysiology, optogenetics, and in vivo two-photon imaging in a mouse model of NIHL, we characterized changes in evoked thalamocortical (TC) synaptic input strength, intrinsic excitability, and sound response properties. We found that TC input was initially equivalent between ETs and CTs, then shifted to CT-dominant one day after noise exposure. This shift renormalized to equivalent seven days after noise exposure and was associated with a transient increase in both the quantal size (q) in TC[->]CT synapses and intrinsic CT suprathreshold excitability. ETs maintained stable intrinsic properties and showed minor changes in their TC input. In vivo imaging revealed that CTs displayed a persistent elevation in sound intensity thresholds, whereas ETs transiently shifted their best frequency representation and reduced their responsiveness to high-frequency tones one day after NIHL, followed by recovery at seven days. Together, our findings highlight cell-type-specific plasticity mechanisms in deep-layer cortical neurons, enhance our understanding of cortical adaptation to peripheral damage, and highlight targets for developing therapeutic strategies to mitigate hearing loss and related disorders such as tinnitus and hyperacusis. Short AbstractPeripheral damage drives auditory cortex (ACtx) plasticity, but the underlying synaptic and cellular mechanisms remain poorly understood. We used a combination of in vitro slice electrophysiology, optogenetics, and in vivo two-photon imaging to investigate layer 5 extratelencephalic (ET) and layer 6 corticothalamic (CT) neuronal plasticity in mice, following noise-induced hearing loss (NIHL). Thalamocortical (TC) input was initially balanced between CTs and ETs but shifted to CT-dominant one day post-NIHL and then normalized by day seven. This transient shift was accompanied by increased quantal size and suprathreshold excitability in CTs, with minimal changes in ETs. In vivo, CTs exhibited persistent elevation in sound intensity thresholds, while ETs showed a transient shift in frequency tuning and reduced high-frequency responsiveness that recovered within a week. These findings reveal distinct, cell-type-specific plasticity mechanisms in deep-layer ACtx neurons following peripheral damage and highlight potential targets for treating hearing loss-related disorders such as tinnitus and hyperacusis.

neuroscience↗

bioRxiv2025

Pupil-linked arousal differentially modulates cell-type-specific sensory processing

Arousal is a ubiquitous influence on the brain that fluctuates during wakefulness and modulates sensation and perception. These fluctuations impact membrane potential, cortical state, and sensory encoding, yet prior studies report inconsistent effects, likely due to averaging across heterogeneous cell types. To resolve this, we combined two-photon calcium imaging and pupillometry in awake mice to examine arousal-related activity in excitatory subpopulations of the auditory cortex: intratelencephalic (IT), extratelencephalic (ET), and corticothalamic (CT) neurons. Pupil-linked arousal modulated all cell types through diverse linear and non-linear response motifs. ET neurons showed significant multiplicative and additive gain modulation, with enhanced response magnitude and encoding but reduced frequency selectivity. CT and L2/3 neurons exhibited inverted-U relationships between arousal and both response strength and decoding accuracy, while IT neurons were minimally affected. These patterns closely tracked changes in population-level reliability, revealing a mechanistic link between internal state and the stability of sensory representations.

neuroscience↗

bioRxiv2024

Primary auditory cortex is necessary for the acquisition and expression of categorical behavior

The primary auditory cortex (ACtx) is critically involved in the association of sensory information with specific behavioral outcomes. Such sensory-guided behaviors are necessarily brain-wide endeavors, requiring a plethora of distinct brain areas, including those that are involved in aspects of decision making, motor planning, motor initiation, and reward prediction. ACtx comprises a number of distinct excitatory cell-types that allow for the brain-wide propagation of behaviorally-relevant sensory information. Exactly how ACtx involvement changes as a function of learning, as well as the functional role of distinct excitatory cell-types is unclear. Here, we addressed these questions by designing a two-choice auditory task in which water-restricted, head-fixed mice were trained to categorize the temporal rate of a sinusoidal amplitude modulated (sAM) noise burst and used transient cell-type specific optogenetics to probe ACtx necessity across the duration of learning. Our data demonstrate that ACtx is necessary for the ability to categorize the rate of sAM noise, and this necessity remains stable across learning. ACtx silencing substantially altered the behavioral strategies used to solve the task by introducing a fluctuating choice bias and increasing dependence on prior decisions. Furthermore, ACtx silencing did not impact the animals motor report, suggesting that ACtx is necessary for the conversion of sensation to action. Targeted inhibition of both intratelencephalic and extratelencephalic projections on just 20% of trials had a modest effect on task performance, but significantly degraded learning. Taken together, our data shows that ACtx plays a critical role in both the acquisition and expression of categorical behavior, and that distinct excitatory projections play important roles in learning and plasticity.

neuroscience↗