T-type Ca 2+ channels mediate a critical period of plasticity in adult-born granule cells.

Adult-born granule cells (abGCs) exhibit a transient period of elevated synaptic plasticity that plays an important role in hippocampal function. Various mechanisms have been implicated in this critical period for enhanced plasticity, including minimal GABAergic inhibition and high intrinsic excitability conferred by T-type Ca2+ channels. Here we assess the contribution of synaptic inhibition and intrinsic excitability to long-term potentiation (LTP) in abGCs of adult male and female mice using perforated patch recordings. We show that the timing of critical-period plasticity is unaffected by intact GABAergic inhibition such that 4-6 week-old abGCs exhibit LTP that is absent by 8 weeks. Blocking GABAA receptors, or partial blockade of GABA release from PV and nNos-expressing interneurons by a µ opioid receptor agonist, strongly enhances LTP in 4-week-old GCs, suggesting that minimal inhibition does not underlie critical period plasticity. Instead, the closure of the critical period coincides with a reduction in the contribution of T-type Ca2+ channels to intrinsic excitability, and a selective T-type Ca2+ channel antagonist prevents LTP in 4-week-old but not mature GCs. Interestingly, whole-cell recordings that facilitate T-type Ca2+ channel activity in mature GCs unmasks LTP (with inhibition intact) that is also sensitive to a T-type Ca2+ channel antagonist, suggesting T-type channel activity in mature GCs is suppressed by native intracellular signaling. Together these results show that abGCs use T-type channels to overcome inhibition, providing new insight into how high intrinsic excitability provides young abGCs a competitive advantage for experience-dependent synaptic plasticity. Significance statement Adult-born granule cells (abGCs) exhibit a transient period of elevated synaptic plasticity that is thought to play an important role in hippocampal function. Here we address the cellular mechanisms that underlie this 'critical period' for plasticity. We show that the closure of the critical period corresponds with loss of intrinsic excitability mediated by T-type Ca2+ channels and that T-type Ca2+ channels promote long-term synaptic plasticity in abGCs despite strong GABAA receptor-mediated inhibition. Regulation of Ca2+ channel function contributes to the loss of excitability and LTP mediated by T-type channels in mature GCs. These results provide insight into how intrinsic excitability and inhibition contribute to plasticity in the dentate gyrus.