Biology subjects

Mol, W.

Publications and source records attributed to Mol, W..

3 recordsLinked to original sources

bioRxiv2024

Learning Impairments in Fmr1-/- mice on an Audio-Visual Temporal Pattern Discrimination Task.

Estimating time and making predictions is integral to our experience of the world. Given the importance of timing to most behaviors, disruptions in temporal processing and timed performance are reported in a number of neuropsychiatric disorders such as Schizophrenia, Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), and Attention-deficit Hyperactivity Disorder (ADHD). Symptoms that implicitly include disruption in timing are atypical turn-taking during social interactions, unusual verbal intonations, poor reading, speech and language skills, inattention, delays in learning, and difficulties making predictions. Currently, there are no viable treatments for these symptoms, the reason being the underlying neural dysfunction that contributes to timing deficits in neuropsychiatric disorders is unknown. To address this unknown, we have designed a novel Temporal Pattern Discrimination Task (TPSD) for awake-behaving mice. Stimuli consist of audiovisual stimuli that differ in duration. Compared to Wild-Type (WT) mice, Fmr1-/- mice, a well-established mouse model of FXS, showed significant impairment in learning the TPSD task, as evidenced by reduced discriminability indices and atypical licking patterns. Often sensory information is multimodal and indeed studies show that learning in humans and rodents improves with multimodal stimuli than with unimodal stimuli. To test how the multimodal nature of stimuli impacted performance of Fmr1-/- mice, following training on the audiovisual stimuli, we tested mice on audio-only or visual-only stimuli. While WT mice showed significant disruption in performance when tested on unimodal stimuli, Fmr1-/- mice displayed equivalent performance on visual-only stimuli when compared to the multimodal task. Our novel task captures timing difficulties and multisensory integration issues in Fmr1-/- mice and provides an assay to examine the associated neural dysfunction.

animal behavior and cognition↗

bioRxiv2024

Temporal information of subsecond sensory stimuli in primary visual cortex is encoded via high dimensional population vectors.

Whether in music, language, baking, or memory, our experience of the world is fundamentally linked to time. However, it is unclear how temporal information is encoded, particularly in the range of milliseconds to seconds. Temporal processing at this scale is critical to prediction and survival, such as in a prey anticipating not only where a charging predator will go but also when the predator will arrive at that location. Several models of timing have been proposed that suggest that either time is encoded intrinsically in the dynamics of a network or that time is encoded by mechanisms that are explicitly dedicated to temporal processing. To determine how temporal information is encoded, we recorded neural activity in primary visual cortex (V1) as mice (male and female) performed a goal directed sensory discrimination task, in which patterns of subsecond stimuli differed only in their temporal profiles. We found that temporal information was encoded in the changing population vector of the network and that the space between these vectors was maximized in learned sessions. Our results suggest that temporal information in the subsecond range is encoded intrinsically and does not rely upon specialized timing mechanisms. SIGNIFICANCE STATEMENTOur experience of the world is fundamentally linked to time, but it is unclear how temporal information is encoded, particularly in the range of milliseconds to seconds. Using a sensory discrimination task in which patterns of subsecond stimuli differed in their temporal profiles, we found that primary visual cortex encodes temporal information via the changing population vector of the network. As temporal processing via population encoding has been shown to rely on inhibitory activity in computational models, our results may provide insight into temporal processing deficits in disorders such as autism spectrum disorder in which there is inhibitory-excitatory imbalance. Furthermore, our results may underlie processing of higher-order sensory stimuli, such as language, that are characterized by complex temporal sequences.

neuroscience↗

bioRxiv2022

Cortical Circuit Mechanisms of Multimodal Temporal Pattern Discrimination

Discriminating between temporal features in sensory stimuli is critical to complex behavior and decision making. However, how sensory cortical circuit mechanisms contribute to discrimination between subsecond temporal components in sensory events is unclear. To elucidate the mechanistic underpinnings of timing in primary visual cortex (V1), we recorded from V1 using 2-photon calcium imaging in awake-behaving mice performing a go/no-go discrimination timing task, which was composed of patterns of subsecond audio-visual stimuli. In both conditions, activity during the early stimulus period was temporally coordinated with the preferred stimulus. However, while network activity increased in the preferred condition, network activity was increasingly suppressed in the nonpreferred condition over the stimulus period. Our results demonstrate that discrimination between subsecond intervals that are contained in rhythmic patterns can be accomplished by local networks and suggest the contribution of neural resonance as a mechanism.

neuroscience↗