Neuroscience
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Disturbance in synaptic excitatory and inhibitory (E/I) transmission in the prefrontal cortex is considered a critical factor for cognitive dysfunction, a core symptom in schizophrenia. However, the cortical network pathophysiology induced by E/I imbalance is not well characterized, and an effective therapeutic strategy is lacking. In this study, we simulated imbalanced cortical network by using mice with parvalbumin neuron (PV) specific knockout of GluA1 (AMPA receptor subunit 1) (Gria1-PV KO) as an experimental model. ⋯ Our results suggest that PV-specific deletion of GluA1 might be an experimental approach for back translating the E/I imbalance observed in schizophrenic patients. Our work offers a systematic workflow to understand the effect of GlyT1 inhibition in restoring cortical network activity from single cells to local brain circuitry. This study highlights that selectively boosting NMDA receptor-mediated excitatory drive to enhance the network inhibitory transmission from interneurons to pyramidal neurons (PYs) is a potential therapeutic strategy for restoring E/I imbalance-associated cognitive-related abnormality.
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The ventral midbrain is the primary source of dopamine- (DA) expressing neurons in most species. GABA-ergic and glutamatergic cell populations are intermixed among DA-expressing cells and purported to regulate both local and long-range dopamine neuron activity. Most work has been conducted in rodent models, however due to evolutionary expansion of the ventral midbrain in primates, the increased size and complexity of DA subpopulations warrants further investigation. ⋯ Putative GABAergic neurons were fewer overall, and evenly dispersed across the DA subpopulations (GAD67 = 71,215 ± 5663; A10 = 16,836 ± 2743; A9 = 24,855 ± 3144 and A8 = 12,633 ± 3557). Calculating the GAD67/TH ratio for each subregion revealed differential balances of these two cell types across the DA subregions. The A8 subregion had the highest complement of GAD67-positive neurons compared to TH-positive neurons (1:1), suggesting a potentially high capacity for GABAergic inhibition of DA output in this region.
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Interlimb coordination deteriorates as a result of aging. Due to its ubiquity in daily life, a greater understanding of the underlying neurophysiological changes is required. Here, we combined electroencephalography time-frequency spectral power and functional connectivity analyses to provide a comprehensive overview of the neural dynamics underlying the age-related deterioration of interlimb coordination involving all four limbs. ⋯ Overall, spectral results suggest that enhanced beta desynchronization in older adults reflects a successful compensatory mechanism to cope with increased difficulty during complex interlimb coordination. Functional connectivity results suggest that theta and alpha band connectivity are prone to respectively task- and age-related modulations. Future work could target these spectral and functional connectivity dynamics through noninvasive brain stimulation to potentially improve interlimb coordination in older adults.