Role of Medial Prefrontal Cortical Neurons and Oxytocin Modulation in the Establishment of Social Buffering

Fear-related behaviors are rigidly controlled by the medial prefrontal cortex (mPFC). The mPFC is activated by the prosocial hormone oxytocin, which plays an important role in social buffering. We used a slice patch current-clamp recording in single- and pair-exposed rats who were subjected to electric shocks, to determine the cellular mechanism of the action of oxytocin in the mPFC under social buffering conditions. Pair-exposed rats showed a significant reduction in both freezing and passive avoidance behaviors compared to single-exposed rats. It was observed that input resistance in pyramidal neurons decreased in both single- and pair-exposed rats than naïve rats, but input resistance in interneurons increased in pair-exposed rats than single-exposed rats. We found that the number of action potential (AP) spikes in the mPFC pyramidal neurons decreased significantly in pair-exposed rats than in single-exposed rats. The pyramidal neurons in the mPFC were similarly regulated by oxytocin in singleand pair-exposed rats, while the number of AP spikes in interneurons by oxytocin decreased in single-exposed rats, but there was no significant change in pair-exposed rats. Therefore, our findings reveal that a decrease in mPFC pyramidal neuronal activity in pair-exposed rats through social interaction induces a reduction in fear-related behavior via obstruction of fear-memory formation; however, no such reduction was observed in single-exposed rats. Moreover, we suggest that the oxytocin-mediated decrease in neuronal activity in the mPFC could facilitate social buffering.

A Novel COL4A1 Mutation in a Neonate with Intrauterine Intraventricular Hemorrhage and Porencephaly

Collagen type IV alpha 1 (COL4A1) plays an important role in construction of the basement membranes of all human tissues, especially vessels. Mutations in COL4A1 lead to various multisystemic dysfunctions, including hereditary porencephaly, hemorrhagic stroke, hemiplegia, cerebral small vessel disease, and nephropathy. In this study, we describe a neonatal case featuring a novel de novo COL4A1 mutation, manifesting as fetal intraventricular hemorrhage and porencephaly. This patient is one of the youngest to have been diagnosed with the most severe phenotype. Our experience may assist clinicians in the diagnosis and management of this extremely rare genetic condition.

Modulation of Dopaminergic Neuronal Excitability by Zinc through the Regulation of Calcium-related Channels

Depending on the intracellular buffering of calcium by chelation, zinc has the following two apparent effects on neuronal excitability: enhancement or reduction. Zinc increased tonic activity in the depolarized state when neurons were intracellularly dialyzed with EGTA but attenuated the neuronal activity when BAPTA was used as an intracellular calcium buffer. This suggests that neuronal excitability can be modulated by zinc, depending on the internal calcium buffering capacity. In this study, we elucidated the mechanisms of zinc-mediated alterations in neuronal excitability and determined the effect of calcium-related channels on zinc-mediated alterations in excitability. The zinc-induced augmentation of firing activity was mediated via the inhibition of small-conductance calcium-activated potassium (SK) channels with not only the contribution of voltage-gated L-type calcium channels (VGCCs) and ryanodine receptors (RyRs), but also through the activation of VGCCs via melastatin-like transient receptor potential channels. We suggest that zinc modulates the dopaminergic neuronal activity by regulating not only SK channels as calcium sensors, but also VGCCs or RyRs as calcium sources. Our results suggest that the cytosolic calcium-buffering capacity can tightly regulate zinc-induced neuronal firing patterns and that local calcium-signaling domains can determine the physiological and pathological state of synaptic activity in the dopaminergic system.