No abstract

Transcranical direct current stimulation (tDCS) is a treatment known to ameliorate various neurological conditions and enhance memory and cognition in humans. tDCS has gained traction for its potential therapeutic value; however, little is known about its mechanism of action. Using a transgenic mouse expressing G-CaMP7 in astrocytes and a subpopulation of excitatory neurons, we find that tDCS induces large-amplitude astrocytic Ca2+ surges across the entire cortex with no obvious changes in the local field potential. Moreover, sensory evoked cortical responses are enhanced after tDCS. These enhancements are dependent on the alpha-1 adrenergic receptor and are not observed in IP3R2 (inositol trisphosphate receptor type 2) knockout mice, in which astrocytic Ca2+ surges are absent. Together, we propose that tDCS changes the metaplasticity of the cortex through astrocytic Ca2+/IP3 signalling.

No abstract

Mice lacking a synaptic isoform of glutamic acid decarboxylase (GAD65) do not exhibit ocular dominance plasticity unless an appropriate level of GABAergic transmission is restored by direct infusion of benzodiazepines into the brain. To better understand how intracortical inhibition triggers experience-dependent changes, we dissected the precise timing requirement for GABA function in the monocular deprivation (MD) paradigm. Diazepam (DZ) or vehicle solution was infused daily before and/or during 4 d of MD in GAD65 knock-out mice. Extracellular single-unit recordings from the binocular zone of visual cortex were performed at the end of deprivation. We found that a minimum treatment of 2 d near the beginning of MD was sufficient to fully activate plasticity but did not need to overlap the deprivation per se. Extended delay after DZ infusion eventually led to loss of plasticity accompanied by improved intrinsic inhibitory circuit function. Two day DZ treatment just after eye opening similarly closed the critical period prematurely in wild-type mice. Raising wild-type mice in complete darkness from birth delayed the peak sensitivity to MD as in other mammals. Interestingly, 2 d DZ infusion in the dark also closed the critical period, whereas equally brief light exposure during dark-rearing had no such effect. Thus, enhanced tonic signaling through GABA(A) receptors rapidly creates a milieu for plasticity within neocortex capable of triggering a critical period for ocular dominance independent of visual experience itself.