Biology subjects

Barkat, T. R.

Publications and source records attributed to Barkat, T. R..

5 recordsLinked to original sources

bioRxiv2025

Cortical neuroprostheses improve auditory coding and perception compared to cochlear implants

Cochlear implants have transformed the treatment of hearing loss by enabling auditory perception through direct electrical stimulation of the auditory nerve. However, their effectiveness can be limited in noisy environments, for fine frequency resolution, and in patients lacking an intact auditory nerve. The auditory cortex offers a promising alternative target for neuroprosthetic stimulation, but it remains unclear whether direct cortical input can evoke percepts with the complexity and structure of natural sounds. Here we show that surface cortical implants in mice support robust and flexible auditory behaviour, surpassing cochlear implants in tasks requiring fine spectral, temporal, and noise-resistant discrimination. We also show that animals generalize seamlessly between cortical and acoustic stimuli without additional training, indicating that cortical stimulation can generate interpretable, sound-like percepts. Electrophysiological recordings revealed that cortical stimulation drives spatially and temporally structured neural activity in auditory cortex, resembling responses to natural sound. These findings establish that the auditory cortex can interpret spatially and temporally patterned electrical input in a behavioural relevant way. By linking neuroprosthetic stimulation to naturalistic neural representations and behavioural generalization, this work provides a mechanistic and functional foundation for cortical auditory neuroprostheses and points toward new strategies for restoring hearing through direct brain stimulation.

neuroscience↗

bioRxiv2024

Top-down inputs are controlled by somatostatin-expressing interneurons during associative learning

Associative learning links sensory signals to their behavioral meaning by combining bottom-up inputs with top-down contextual information, enabling decision-making based on expected outcomes. It triggers plastic changes of neuronal responses in both excitatory and inhibitory cell populations. However, the role of inhibition in shaping this plasticity remains debated. Here we used chronic extracellular electrophysiology and optogenetic manipulation of inhibitory neurons and top-down inputs in mice learning an auditory discrimination task. We found that learning enhances stimulus selectivity in a subset of neurons in the primary auditory cortex. Interestingly, somatostatin-expressing (SST) interneurons decrease their response to the rewarded cue and bidirectionally regulate associative learning. More specifically, an increased activity of SST neurons impairs learning by altering bottom-up signaling, whereas the reduction of their activity facilitates learning by gating top-down inputs from the orbitofrontal cortex. These findings demonstrate that inhibition plays a critical role in gating top-down inputs to primary sensory cortices involved in associative learning.

neuroscience↗

bioRxiv2024

Curriculum Learning: sequential acquisition of task complexity enhances neuronal discriminability

Curriculum Learning (CL) is a strategy where concepts with increasing complexity are acquired sequentially. Despite its widespread application, its putative neural mechanisms are poorly understood. In this study, using a multi-staged Go/No-Go auditory discrimination paradigm for mice, we show that CL improves and accelerates learning in a unidirectional way. By combining behavioral data with in vivo electrophysiological recordings of the auditory cortex, we demonstrate that neuronal discriminability is enhanced with sequential training. This improvement suggests that CL involves a convergence of common discriminable features in the auditory stimuli shared across tasks of different complexity. Our findings uncover specific properties of CL at the level of neuronal discriminability, distinguishing it from other forms of learning strategies.

neuroscience↗

bioRxiv2022

Soluble amyloid-β precursor peptide does not regulate GABAB receptor activity

Amyloid-{beta} precursor protein (APP) regulates neuronal activity through the release of secreted APP (sAPP) acting at cell-surface receptors. APP and sAPP were reported to bind to the extracellular sushi domain 1 (SD1) of GABAB receptors (GBRs). A 17 amino-acid peptide (APP17) derived from APP was sufficient for SD1 binding and shown to mimic the inhibitory effect of sAPP on neurotransmitter release and neuronal activity. The functional effects of APP17 and sAPP were similar to those of the GBR agonist baclofen and blocked by a GBR antagonist. These experiments led to the proposal that sAPP activates GBRs to exert its neuronal effects. However, whether APP17 and sAPP indeed influence classical GBR signaling pathways in heterologous cells was not analyzed. Here, we confirm that APP17 binds to GBRs with nanomolar affinity. However, biochemical and electrophysiological assays indicate that APP17 does not influence GBR activity in heterologous cells. Moreover, we found no evidence for APP17 regulating K+ currents in cultured neurons, neurotransmitter release in brain slices, or neuronal activity in vivo. Our results show that APP17 is not a functional GBR ligand and indicate that sAPP exerts neuronal effects through receptors other than GBRs.

neuroscience↗

bioRxiv2021

Emergence and function of cortical offset responses in sound termination detection

Offset responses in auditory processing appear after a sound terminates. They arise in neuronal circuits within the peripheral auditory system, but their role in the central auditory system remains unknown. Here we ask what the behavioural relevance of cortical offset responses is and what circuit mechanisms drive them. At the perceptual level, our results reveal that experimentally minimizing auditory cortical offset responses decreases the mouse performance to detect sound termination, assigning a behavioural role to offset responses. By combining in vivo electrophysiology in the auditory cortex and thalamus of awake mice, we also demonstrate that cortical offset responses are not only inherited from the periphery but also amplified and generated de novo. Finally, we show that offset responses code more than silence, including relevant changes in sound trajectories. Together, our results reveal the importance of cortical offset responses in encoding sound termination and detecting changes within temporally discontinuous sounds crucial for speech and vocalization.

neuroscience↗