Eye opening, a natural and timed event during animal development, influences cortical circuit assembly and maturation; yet, little is known about its precise effect on inhibitory synaptic connections. Here, we show that coinciding with eye opening, the strength of unitary inhibitory postsynaptic currents (uIPSCs) from somatostatin-expressing interneurons (Sst-INs) to nearby excitatory neurons, but not interneurons, sharply decreases in layer 2/3 of the mouse visual cortex. In contrast, the strength of uIPSCs from fast-spiking interneurons (FS-INs) to excitatory neurons significantly increases during eye opening. More importantly, these developmental changes can be prevented by dark rearing or binocular lid suture, and reproduced by the artificial opening of sutured lids. Mechanistically, this differential maturation of synaptic transmission is accompanied by a significant change in the postsynaptic quantal size. Together, our study reveals a differential regulation in GABAergic circuits in the cortex driven by eye opening may be crucial for cortical maturation and function.

Melatonin (MT) may work as a neuromodulator through the associated MT receptors in the central nervous system. Previously, our studies have shown that MT increased the I K current via a G protein-related pathway. In the present study, patch-clamp whole-cell recording, transwell migration assays and organotypic cerebellar slice cultures were used to examine the effect of MT on granule cell migration. MT increased the I K current amplitude and migration of granule cells. Meanwhile, TEA, the I K channel blocker, decreased the I K current and slowed the migration of granule cells. Furthermore, the effects of MT on the I K current and cell migration were not abolished by pre-incubation with P7791, a specific antagonist of MT 3 R, but were eliminated by the application of the MT 2 R antagonists K185 and 4-P-PDOT. I K current and cell migration were decreased by the application of dibutyryl cyclic AMP (dbcAMP), which was in contrast to the MT effect on the I K current and cell migration. Incubation with dbcAMP essentially blocked the MT-induced increasing effect. Moreover, incubation of isolated cell cultures in the MT-containing medium also decreased the cAMP immunoreactivity in the granule cells. It is concluded, therefore, that I K current, downstream of a cAMP transduction pathway, mediates the migration of rat cerebellar granule cells stimulated by MT.

Transplantation of embryonic γ-aminobutyric acid (GABA)ergic neurons has been shown to modify disease phenotypes in rodent models of neurologic and psychiatric disorders. However, whether transplanted interneurons modulate fear memory remains largely unclear. Here, we report that transplantation of embryonic interneurons into the amygdala does not alter host fear memory formation. Yet approximately 2 weeks after transplantation, but not earlier or later, extinction training produces a marked reduction in spontaneous recovery and renewal of fear response. Further analyses reveal that transplanted interneurons robustly form functional synapses with neurons of the host amygdala and exhibit similar developmental maturation in electrophysiological properties as native amygdala interneurons. Importantly, transplanted immature interneurons reduce the expression of perineuronal nets, promote long-term synaptic plasticity, and modulate both excitatory and inhibitory synaptic transmissions of the host circuits. Our findings demonstrate that transplanted immature interneurons modify amygdala circuitry and suggest a previously unknown strategy for the prevention of extinction-resistant pathological fear.

No abstract

Effects of post-weaning isolation on depressive- and anxiety-like behaviors in rodents have been well studied in the past. However, few studies included both sexes in a single experiment to study the sex difference in this animal model. The present study investigated the effect of post-weaning isolation on anxiety- and depressive-like behaviors in both male and female C57BL/6 J mice. Mice were individually or grouped housed from postnatal day 21 for 5 weeks until behavioral tests began. The results showed that social isolation resulted in increased anxiety in the open field. Isolated-reared female, but not male mice showed an increased transition between two compartments in the light-dark box and a decreased immobile time in the forced swim test. We conclude that post-weaning isolation has a sex-specific effect on emotional behaviors.