Biology subjects

Kampa, B.

Publications and source records attributed to Kampa, B..

4 recordsLinked to original sources

bioRxiv2024

Dnmt1-deficiency in PV interneurons alters cortical circuit function and leads to depression-like behavior

Neuropsychiatric disorders, including major depressive disorder (MDD), are highly prevalent in modern society, arising from a complex interplay of genetic and environmental factors. Alterations in the function of cortical inhibitory GABAergic interneurons, along with dysregulations of epigenetic signatures and key regulators such as DNA methyltransferase 1 (DNMT1), have been implicated in these conditions. Through its role in catalyzing DNA methylation, DNMT1 modulates the synaptic activity of parvalbumin-expressing (PV) interneurons, which are essential for cortical inhibition. However, the functional consequences of DNMT1 activity in cortical interneurons at the network level and its impact on behavior remain unknown and must be explored to fully understand the disease implications of dysregulated DNMT1 expression and function. To address this, we utilized a conditional knockout mouse model with Dnmt1 deletion in PV interneurons. Our findings reveal that a Dnmt1 deficiency leads to increased spontaneous firing rates of cortical neurons, reduced cortical gamma oscillations, and altered visually evoked neural responses. Despite intact sensory perception, Dnmt1-deficient mice exhibited reduced physical activity, heightened anxiety-like behavior, and signs of anhedonia and apathy, which represent core features of MDD. These results underscore the critical role of DNMT1 in PV interneuron function and identify it as a potential target for MDD research.

neuroscience↗

bioRxiv2024

Ongoing activation of visual cortex and superior colliculus in the rd10 mouse model of retinitis pigmentosa

Efforts in vision restoration have been focused on a condition called Retinitis Pigmentosa, where photoreceptors in the retina degenerate while the rest of the visual pathway remain mostly intact. Retinal implants that replace the phototransduction process by stimulating retinal ganglion cells have shown promising but limited results in patients so far. Apart from technical limitations, cross-modal plasticity of visual areas might contribute to this problem. We therefore investigated if the primary visual cortex (V1) of the rd10 mouse model for retinal degeneration became more sensitive to auditory or tactile sensory inputs, potentially hindering retinal stimulation. After reaching complete blindness confirmed by the lack of optomotor responses, activity in visual cortex and superior colliculus (SC) was recorded using Neuropixels probes. While we could not find any significant differences in tactile or auditory responses compared to wildtype mice, the local field potential revealed distinct oscillatory events (0.5 - 6 Hz) in V1 and SC resembling previously observed aberrant activity in the retina of rd10 mice. Further absence of cross-modal plasticity was confirmed by a lacking increase in zif268 expression in V1 after tactile stimulation. We therefore propose that aberrant retinal activity is transmitted to higher visual areas where it prevents cross-modal changes.

neuroscience↗

bioRxiv2024

Temporal Dynamics of Neocortical Development in Organotypic Mouse Cultures: A Comprehensive Analysis

Murine organotypic brain slice cultures have been widely used in neuroscientific research and are offering the opportunity to study neuronal function under normal and disease conditions. Despite the brought application, the mechanisms governing the maturation of immature cortical circuits in vitro are not well understood. In this study, we present a detailed investigation into the development of the neocortex in vitro. Utilizing a holistic approach, we studied organotypic whole-hemisphere brain slice cultures from postnatal mice and tracked the development of the somatosensory area over a five-week period. Our analysis revealed the maturation of passive and active intrinsic properties of pyramidal cells together with their morphology, closely resembling in vivo development. Detailed Multi-electrode array (MEA) electrophysiological assessments and RNA expression profiling demonstrated stable network properties by two weeks in culture, followed by the transition of spontaneous activity towards more complex patterns including high-frequency oscillations. However, weeks 4 and 5 exhibited increased variability and initial signs of neuronal loss, highlighting the importance of considering developmental stages in experimental design. This comprehensive characterization is vital for understanding the temporal dynamics of the neocortical development in vitro, with implications for neuroscientific research methodologies, particularly in the investigation of diseases such as epilepsy and other neurodevelopmental disorders.

neuroscience↗

bioRxiv2023

Broadband visual stimuli improve neuronal representation and sensory perception

Natural scenes consist of complex feature distributions that shape neural responses and perception. However, in contrast to single features like stimulus orientations, the impact of broadband feature distributions remains unclear. We, therefore, presented visual stimuli with parametrically-controlled bandwidths of orientations and spatial frequencies to awake mice while recording neural activity in their primary visual cortex (V1). Increasing orientation but not spatial frequency bandwidth strongly increased the number and response amplitude of V1 neurons. This effect was not explained by single-cell orientation tuning but rather a broadband-specific relief from center-surround suppression. Moreover, neurons in deeper V1 and the superior colliculus responded much stronger to broadband stimuli, especially when mixing orientations and spatial frequencies. Lastly, broadband stimuli increased the separability of neural responses and improved the performance of mice in a visual discrimination task. Our results show that surround modulation increases neural responses to complex natural feature distributions to enhance sensory perception.

neuroscience↗