Biology subjects

Atilgan, H.

Publications and source records attributed to Atilgan, H..

7 recordsLinked to original sources

bioRxiv2025

Deep three-photon functional imaging in the mouse cortex with adaptive optics

Three-photon (3P) microscopy enables functional non-invasive single-cell resolution imaging at greater depths than any other technique. A key challenge of deep imaging is tissue-induced optical aberration, which reduces the excitation confinement. Adaptive optics use deformable mirrors to compensate for optical distortions, hence correcting these aberrations. Here, we present a practical adaptive optics-assisted 3P imaging system for functional imaging in the mouse brain during behavior. We introduce hierarchical corrections that sequentially target aberrations caused by the microscope system, the cranial window, and tissue depth. We demonstrate the utility of this strategy in the prelimbic cortex, where large vasculature near the midline causes aberrations, and in the lateral somatosensory cortex, where side access leads to distinct wavefront distortions. In both regions, adaptive optics significantly improved imaging performance, restoring cellular visibility near vasculature and enhancing signal-to-noise ratio. Our work provides a practical framework for utilizing adaptive optics to improve 3P imaging during behavior.

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bioRxiv2024

The claustrum enhances neural variability by modulating the responsiveness of the prefrontal cortex

The claustrum is recognized for its significant impact on various cognitive functions and its extensive connections with other brain regions, yet its functional role remains to be fully understood. Here, we utilized an optogenetic approach to investigate the claustrums influence on neuronal activity within the dorsal prefrontal cortex (dPFC) of mice. We conducted two-photon calcium imaging to assess dPFC cell responses during exposure to visual stimuli and widefield photostimulation of claustrum axons embedded in the dPFC. We identified three distinct subpopulations of neurons -- sensory responsive, opto responsive, and opto-boosted cells -- each exhibiting unique response dynamics to combined visual and optogenetic stimuli. Our findings reveal that stimulation of claustrum axons can normalize neuronal responsiveness, while enhancing neural variability, and significantly increasing network homogeneity. Training in a Pavlovian task showed that while enhanced variability with claustrum axon stimulation in neural responses persists, training does not further increase this variability but instead leads to greater network homogeneity. Additionally, we also performed claustrum axon silencing experiments that revealed that the claustrum may operate bidirectionally to maintain enhanced variability and homogeneity in the prefrontal cortex. These results highlight the crucial role of the claustrum in dynamically modulating dPFC activity, impacting both neuronal variability and network synchronization.

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bioRxiv2023

Auditory training alters the cortical representation of both learned and task irrelevant sound features

Auditory learning is supported by long-term changes in the neural processing of sound. We examined these task-depend changes in auditory cortex by mapping neural sensitivity to timbre, pitch and location cues in trained ferrets (n = 5), and untrained control ferrets (n = 5). Trained animals either identified vowels in a two-alternative forced choice task (n = 3) or discriminated when a repeating vowel changed in identity or pitch (n = 2). Neural responses were recorded under anesthesia in two primary auditory cortical fields and two tonotopically organized non-primary fields. In trained animals, the overall sensitivity to sound timbre was reduced across three cortical fields compared to control animals, but maintained in a non-primary field (the posterior pseudosylvian field). While training did not increase sensitivity to timbre across auditory cortex, it did change the way in which neurons integrated spectral information with neural responses in trained animals increasing their sensitivity to first and second formant frequencies,, whereas in control animals cortical sensitivity to spectral timbre depends mostly on the second formant. Animals trained on timbre identification were required to generalize across pitch when discriminating timbre and their neurons became less modulated by fundamental frequency relative to control animals. Finally, both trained groups showed increased spatial sensitivity and an enhanced response to sound source locations close to the midline, where the loudspeaker was located in the training chamber. These results demonstrate that training elicited widespread alterations in the cortical representation of complex sounds.

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bioRxiv2022

Change point estimation by the mouse medial frontal cortex during probabilistic reward learning

There are often sudden changes in the state of environment. For a decision maker, accurate prediction and detection of change points are crucial for optimizing performance. Still unclear, however, is whether rodents are simply reactive to reinforcements, or if they can be proactive to estimate future change points during value-based decision making. In this study, we characterize head-fixed mice performing a two-armed bandit task with probabilistic reward reversals. Choice behavior deviates from classic reinforcement learning, but instead suggests a strategy involving belief updating, consistent with the anticipation of change points to exploit the task structure. Excitotoxic lesion and optogenetic inactivation implicate the anterior cingulate and premotor regions of medial frontal cortex. Specifically, over-estimation of hazard rate arises from imbalance across frontal hemispheres during the time window before the choice is made. Collectively, the results demonstrate that mice can capitalize on their knowledge of task regularities, and this estimation of future changes in the environment may be a main computational function of the rodent dorsal medial frontal cortex.

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bioRxiv2021

Pupil correlates of decision variables in mice playing a competitive mixed-strategy game

In a competitive game involving an animal and an opponent, the outcome is contingent on the choices of both players. To succeed, the animal must continually adapt to competitive pressure, or else risk being exploited and lose out on rewards. In this study, we demonstrate that head-fixed mice can be trained to play the iterative competitive game matching pennies against a virtual computer opponent. We find that the animals performance is well described by a hybrid computational model that includes Q-learning and choice kernels. Comparing between matching pennies and a non-competitive two-armed bandit task, we show that the tasks encourage animals to operate at different regimes of reinforcement learning. To understand the involvement of neuromodulatory mechanisms, we measure fluctuations in pupil size and use multiple linear regression to relate the trial-by-trial transient pupil responses to decision-related variables. The analysis reveals that pupil responses are modulated by observable variables, including choice and outcome, as well as latent variables for value updating, but not action selection. Collectively, these results establish a paradigm for studying competitive decision-making in head-fixed mice and provide insights into the role of arousal-linked neuromodulation in the decision process.

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bioRxiv2018

Training listeners to detect auditory-visual temporal coherence enhances their ability to exploit visual information for auditory scene analysis

The ability to use temporal relationships between cross-modal cues facilitates perception and behavior. Previously we observed that temporally correlated changes in the size of a visual stimulus and the intensity in an auditory stimulus influenced the ability of listeners to perform an auditory selective attention task (Maddox et al., 2015). In this task participants detected timbral changes in a target sound while ignoring those in a simultaneously presented masker. When the visual stimulus was temporally coherent with the target sound, performance was significantly better than when it was temporally coherent with the masker sound, despite the visual stimulus conveying no task-relevant information. Here, we trained observers to detect audiovisual temporal coherence and asked whether this improved their ability to benefit from visual cues during the auditory selective attention task. We observed these listeners improved performance in the auditory selective attention task and changed the way in which they benefited from a visual stimulus: after training performance was better when the visual stimulus was temporally coherent with either the target or the masker stream, relative to the condition in which the visual stimulus was coherent with neither auditory stream. A second group which trained to discriminate modulation rate differences between temporally coherent audiovisual streams improved task performance, but did not change the way in which they used visual information. A control group did not change their performance between pretest and post-test. These results provide insights into how crossmodal experience may optimize multisensory integration.

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bioRxiv2017

Integration of visual information in auditory cortex promotes auditory scene analysis through multisensory binding

How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a mechanism for binding stimulus features across sensory modalities. Here we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex, via the phase of the local field potential, and is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.

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