Thus, dopamine/D4R ATR inhibitor signaling is a novel zeitgeber that entrains the rhythm of Adcy1 expression and, consequently, modulates the rhythmic synthesis of cyclic AMP in mouse retina. “
“It is well documented that neurofibrillary tangles composed of aggregated tau protein propagate in a predictable pattern in Alzheimer’s disease (AD). The mechanisms underlying the propagation of tau pathology are still poorly understood. Recent studies have provided solid data demonstrating that in several neurodegenerative diseases including AD, the spreading of misfolded protein aggregates in the brain would result from prion-like

cell-to-cell transmission. Consistent with this new concept, recent studies have reported that human tau can be released in the extracellular space by an active process of secretion, and can be endocytosed both in vitro and in vivo. Most importantly, it was reported that the spreading of tau pathology was observed along synaptically connected circuits FG-4592 clinical trial in a transgenic mouse model where human tau overexpression was restricted in the entorhinal cortex. This indicates that secretion of tau by presynaptic neurons and its uptake by postsynaptic neurons

could be the sequential events leading to the propagation of tau pathology in the brain. “
“Within the hippocampus and neocortex, GABA is considered to be excitatory in early development due to a relatively depolarized Cl− reversal potential (ECl). Although the depolarizing nature of synaptic GABAergic events has been well established, it is unknown whether cortical tonic currents mediated by extrasynaptically located GABAA receptors (GABAARs) are also excitatory. Here we examined the development of tonic currents in the neocortex and their effect on neuronal excitability. Mean tonic current, recorded from layer second 5 (L5) pyramidal cells of the mouse somatosensory cortex, is robust in

newborns [postnatal day (P)2–4] then decreases dramatically by the second postnatal week (P7–10 and P30–40). Pharmacological studies, in combination with Western blot analysis, show that neonatal tonic currents are partially mediated by the GABAAR α5 subunit, and probably the δ subunit. In newborns, the charge due to tonic current accounts for nearly 100% of the total GABA charge, a contribution that decreases to < 50% in mature tissue. Current clamp recordings show that tonic current contributes to large fluctuations in the membrane potential that may disrupt its stability. Bath application of 5 μM GABA, to induce tonic currents, markedly decreased cell firing frequency in most recorded cells while increasing it in others. Gramicidin perforated patch recordings show heterogeneity in ECl recorded from P2–5 L5 pyramidal cells.