Prefrontal GABAA(δ)R Promotes Fear Extinction through Enabling the Plastic Regulation of Neuronal Intrinsic Excitability.

Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABAA receptors (GABAARs). GABAARs consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, δ-subunit-containing GABAARs [GABAA(δ)Rs], had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABAAR family. First, the fear extinction in individual mice was positively correlated with the level of GABAA(δ)R expression and function in their mPFC. Second, knockdown of GABAA(δ)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABAA(δ)R-deficient mice also showed fear extinction deficits, and re-expressing GABAA(δ)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABAA(δ)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABAA(δ)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABAA receptors in fear extinction through a route relying on nonsynaptic plasticity.SIGNIFICANCE STATEMENT The medial prefrontal cortex (mPFC) is one of the kernel brain regions engaged in fear extinction. Previous studies have repetitively shown that the GABAA receptor (GABAAR) family in this region act to suppress fear extinction. However, the roles of specific GABAAR subtypes in mPFC are largely unknown. We observed that the GABAAR-containing δ-subunit [GABAA(δ)R], a subtype of GABAARs exclusively situated in the extrasynaptic membrane and mediating the tonic neuronal inhibition, works oppositely to the whole GABAAR family and promotes (but does not suppress) fear extinction. More interestingly, in striking contrast to the synaptic GABAARs that suppress fear extinction by breaking the extinction-evoked plasticity of glutamatergic transmission, the GABAA(δ)R promotes fear extinction through enabling the plastic regulation of neuronal excitability in the infralimbic subregion of mPFC. Our findings thus reveal an unconventional role of GABAA(δ)R in promoting fear extinction through a route relying on nonsynaptic plasticity.

Ant-nest-like Cu2-xSe@C with biomimetic channels boosts the cycling performance for lithium storage.

Controlling the microstructure and composition of electrodes is crucial to enhance their rate capability and cycling stability for lithium storage. Inspired by the highly interconnected network and good mechanical integrity of an ant-nest architecture, herein, a biomimetic strategy is proposed to enhance the electrochemical performance of Cu2-xSe. After facile carbonization and selenization treatments, the 3D Cu-MOF is successfully transformed into the final ant-nest-like Cu2-xSe@C (AN-Cu2-xSe@C). The AN-Cu2-xSe@C is composed of interconnected Cu2-xSe channels with amorphous carbon coated on the outer surface. The 3D interconnected channels within the AN-Cu2-xSe@C provide fast charge transport pathways and enhanced structural integrity to tolerate the large volume fluctuations of Cu2-xSe during cycling. When applied as the anode for lithium storage, the AN-Cu2-xSe@C shows remarkable electrochemical performance with a high capacity of 1452 mA h g-1 after 1200 cycles at 1.0 A g-1 and 879 mA h g-1 after 2500 cycles at 10.0 A g-1, respectively. Mechanism investigations demonstrate that the AN-Cu2-xSe@C experiences complicated conversion-intercalation co-existence reactions upon cycling. The existence of capacitive behaviour (74%) also contributes to the extended cycling performance. Our work offers a new avenue for designing a high performance electrode using the biomimetic concept.