Biology subjects

Hensch, T. K.

Publications and source records attributed to Hensch, T. K..

5 recordsLinked to original sources

bioRxiv2025

Growth charts of infant visual neurodevelopment generalize across global contexts

Normative brain growth charts in early life hold great promise for furthering basic and clinical science. We leverage the rapid, substantial development of visual cortex function that is indexed by visual-evoked potentials (VEP) in electroencephalography to create longitudinal normative growth curves of task-related brain function with 1374 observations contributed by 802 infants (57 to 579 days old) from South Africa, Brazil, and the United States. Site-specific models were cross-validated and showed excellent fits to other sites samples, demonstrating functional growth curves generalize across contexts robustly. Deviations from the normative growth models associated with early environmental and behavioral measures such as prenatal exposures and postnatal cognition. These findings demonstrate the utility of using functional growth charts to understand and potentially act on individual neurodevelopmental trajectories. VEP brain function growth charts represent a new direction for EEG research to support healthy brain development globally.

neuroscience↗

bioRxiv2023

Deficiency in neprilysin causes laminar impairments in the visual cortex

1Neprilysin (Nep) is a membrane-bound zinc-dependent endopeptidase that cleaves a wide variety of small peptides in the body. In the brain, it has gained fame as an important endogenous degrader of amyloid beta peptide, responsible for the pathophysiology of Alzheimers disease. Nep is expressed specifically by parvalbumin (PV)-expressing inhibitory neurons in the adult cortex, the maturation of which regulates critical period plasticity. Given that PV neuron soma and proximal dendrites are primary sites of perineuronal net (PNN) formation, we investigated the role that Nep plays in PNN and PV neuron maturation and cortical development in the mouse visual cortex, using mice whose Nep expression is constitutively knocked out (Nep KO mice). Nep expression is high in young wildtype mice (P10) and is downregulated rapidly throughout postnatal development. It is especially prominent in layer 5 where it is highly expressed by inhibitory neurons and also expressed at low levels by many excitatory neurons. Contrary to our hypothesis, Nep KO mice did not show an alteration in the relative density or gross morphology of PNNs. Instead, Nep KO mice showed reduced maximal activation of L5 after white matter stimulation and decreased number of inhibitory neurons in L4. These laminar defects may lead to impaired development of optomotor acuity in Nep KO mice.

neuroscience↗

bioRxiv2017

Neuronal tracing and analysis by multispectral tracing in densely labeled mouse brain

Accurate and complete neuronal wiring diagrams are necessary for understanding brain function at many scales from long-range interregional projections to microcircuits. Traditionally, light microscopy-based anatomical reconstructions use monochromatic labeling and therefore necessitate sparse labeling to eliminate tracing ambiguity between intermingled neurons. Consequently, our knowledge of neuronal morphology has largely been based on averaged estimations across many samples. Recently developed second-generation Brainbow tools promise to circumvent this limitation by revealing fine anatomical details of many unambiguously identifiable neurons in densely labeled samples. Yet, a means to quantify and analyze the information is currently lacking. Therefore, we developed nTracer, an ImageJ plugin capable of rapidly and accurately reconstructing whole-cell morphology of large neuronal populations in densely labeled brains.

neuroscience↗

bioRxiv2017

Enhanced cross-modal activation of sensory cortex in mouse models of autism

SUMMARYSynesthesia is a condition wherein one sense is evoked by another. Recent studies suggested a higher incidence of synesthesia among people with autism. However, the underlying circuit mechanism of the comorbidity remains unknown partly due to lack of animal models. Here, we measured auditory response of primary visual cortex (V1) in mouse models to estimate the mixture level of their senses. We found that the V1 auditory response exhibits bidirectional cross-modal plasticity and depends on the level of GABA-mediated inhibition. Analysis of the V1 auditory response in autistic BTBR strain revealed its contralateral bias as in primary auditory cortex, and the auditory evoked field potential was enhanced at gamma range. Furthermore, early sound-driven spike modulation of V1 was commonly shifted toward enhancement in three different autism models (BTBR, NL3 R451C, SCN1A R1407X). Disruption of excitatory/inhibitory (E/I) circuit balance is prevalent among autistic people and mouse models. Thus, our results suggest that E/I imbalance may be the common circuit dysfunction for both autism and synesthesia.

neuroscience↗

bioRxiv2017

Developmental dynamics of cross-modality in mouse visual cortex

Maturation of GABAergic circuits in primary visual cortex (V1) opens a critical period (CP), a developmental window of enhanced plasticity for visual functions. However, how inhibition promotes the plasticity remains unclear. Here, we investigated the developmental dynamics of auditory responses and audiovisual interactions in mouse V1. Modulation of V1 spiking activity by a transient sound was temporally dynamic with alternating enhancement and suppression phases. When paired with grating visual stimuli, sound-driven spike enhancement and suppression were weaker and stronger with preferred orientation than with non-preferred orientations, respectively, leading to impaired net orientation selectivity in V1 neurons. Strikingly, the net orientation selectivity was impervious to sound specifically during the CP due to equal total amounts of sound-driven spike enhancements and suppressions. This balance of spike modulations at the CP was achieved by the preferential maturation of sound-driven spike suppression. However, further maturation of sound-driven spike enhancement broke the balance after the CP. Spectral analysis of field potentials revealed the enhancement of a GABA-mediated sound-driven power suppression specifically at CP. Reduction of inhibition by 10-day dark-exposure or genetic deletion of GAD65 gene dampened sound-driven spike suppression in V1. Furthermore, acute suppression of either parvalbumin-expressing (PV) or somatostatinexpressing (SST) neurons suggested their early or late recruitments by sound, respectively. Our results point to the dampened net non-visual sensory influence as one of the functional roles of GABA circuit maturation during a developmental CP. The insensitivity of visual selectivity to sound during the CP may promote functional maturation of V1 as visual cortex.

neuroscience↗