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Dodson, H.

Publications and source records attributed to Dodson, H..

2 recordsLinked to original sources

Complex three-dimensional rearing environments amplify compensatory plasticity following early blindness

The neocortex has a remarkable capacity to alter its functional organization and connectivity in response to sensory loss, particularly if this loss occurs early in life. A key question is whether this cross-modal reorganization is driven by sensory deprivation or by enhanced use of the spared senses. We investigated how different rearing environments shape neural responses in primary somatosensory cortex (S1) of short-tailed opossums (Monodelphis domestica), following elimination of visual inputs through bilateral enucleation in early development. Early blind and sighted littermates were reared in enriched environments to promote active tactile exploration in three-dimensional (3D) space, or in standard laboratory cages. In adulthood, both enriched groups showed adaptive changes in exploration patterns and gap crossing behaviors relative to standard-reared counterparts. Thus, early blind animals showed behavioral compensation when challenged by complex environments. Enriched rearing increased selectivity of S1 neural responses to whisker touch and altered receptive field shapes such that they were less horizontally anisotropic. This shift was strongest in enriched early blind animals, enhancing tuning along the behaviorally relevant horizontal axis more than in standard-reared early blind animals. Thus, alterations in receptive fields of neurons in S1 following early blindness were amplified by environmental complexity. Sighted opossums reared with enrichment also showed similar whisker receptive field plasticity, though to a slightly lower degree. Together, these results demonstrate the strong influence of the rearing environment on reorganization of cortex that processes inputs from the spared senses, underscoring the role of experience in directing compensatory plasticity following early sensory loss. SIGNIFICANCE STATEMENTEnhanced perceptual abilities following early sensory loss are often attributed to cross-modal recruitment of cortex linked to the deprived sense. However, plasticity also occurs within cortical areas representing spared modalities. It remains unresolved whether deprivation alone is sufficient to induce such reorganization, or whether experience using the spared sense is required. We show that enriched rearing amplifies neural coding changes in primary somatosensory cortex after early blindness, shaping receptive field geometry and promoting adaptive behavioral strategies aligned with environmental demands. Comparable changes in sighted animals reared under the same conditions reveal that reliance on touch--rather than visual deprivation alone--drives this neural and behavioral plasticity, supporting the critical role of experience in enhancing functional outcomes after early sensory impairment.

neuroscience↗

Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

The cannabinoid receptor type 1 (CB1R) is a promising therapeutic target for various neurodegenerative diseases, including HIV-1-associated neurocognitive disorder (HAND). However, the therapeutic potential of CB1R by direct activation is limited due to its psychoactive side effects. Therefore, research has focused on indirectly activating the CB1R by utilizing positive allosteric modulators (PAMs). Studies have shown that CB1R PAMs (ZCZ011 and GAT211) are effective in mouse models of Huntingtons disease and neuropathic pain, and hence, we assess the therapeutic potential of ZCZ011 in a well-established mouse model of neuroHIV. The current study investigates the effect of chronic ZCZ011 treatment (14 days) on various behavioral paradigms and the endocannabinoid system in HIV-1 Tat transgenic female and male mice. Chronic ZCZ011 treatment (10 mg/kg) did not alter body mass, locomotor activity, or anxiety-like behavior regardless of sex or genotype. However, differential effects were noted in hot plate latency, motor coordination, and recognition memory in female mice only, with ZCZ011 treatment increasing hot plate latency and improving motor coordination and recognition memory. Only minor effects or no alterations were seen in the endocannabinoid system and related lipids except in the cerebellum, where the effect of ZCZ011 was more pronounced in female mice. Moreover, AEA and PEA levels in the cerebellum were positively correlated with improved motor coordination in female mice. In summary, these findings indicate that chronic ZCZ011 treatment has differential effects on antinociception, motor coordination, and memory, based on sex and HIV-1 Tat expression, making CB1R PAMs potential treatment options for HAND without the psychoactive side effects.

neuroscience↗