The findings suggest that mitochondria in oocytes and preimplantation embryos may be heterogeneous with respect to deltapsim. We propose that high-polarized pericortical mitochondria may have a role in the acquisition of oocyte competence and the regulation of early developmental processes that may be associated with elevated metabolism or intracellular signalling through calcium-induced calcium release pathways.

The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a novel combination of chemogenetics, activity-based neuronal-ensemble labeling, and in vivo electrophysiology, we found that fear extinction learning confers parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) with a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6–12 Hz oscillation and a fear-associated 3–6 Hz oscillation within the BLA. Loss of this competition increases a 3–6 Hz oscillatory signature, with BLA→mPFC directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV-interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning.

It has been suggested that mitochondrial DNA defects that effect metabolic capacity may be a proximal cause of failures in oocyte maturation, fertilization, or early embryonic development. Here, the distribution of mitochondria was examined by scanning laser confocal microscopy in living human pronuclear oocytes and cleavage stage embryos, followed either by measurements of the net ATP content of individual blastomeres or anti-tubulin immunofluorescence to determine the relationship between mitochondrial distribution and microtubular organization. The results indicate that specific patterns of perinuclear mitochondrial aggregation and microtubular organization are related, and that asymmetrical mitochondrial distributions at the pronuclear stage can result in some proportion of blastomeres with reduced mitochondrial inheritance and diminished ATP generating capacity. While the inability to divide appears to be a development consequence for an affected blastomere, for the embryo, reduced competence may occur during cleavage if several blastomeres inherit a mitochondrial complement inadequate to support normal cellular functions. The findings provide a possible epigenetic explanation for the variable developmental ability expressed within cohorts of morphologically normal early cleavage stage human embryos obtained by in-vitro fertilization.

The development of neural circuits relies on axon projections establishing diverse, yet well-defined, connections between areas of the nervous system. Each projection is formed by growth cones (GCs), subcellular specializations at the tips of growing axons, encompassing sets of molecules that control projection-specific growth, guidance, and target selection1. To investigate the set of molecules within native GCs forming specific connections, we developed GC Sorting and Subcellular RNA-Proteome Mapping, an approach that identifies and quantifies local transcriptomes and proteomes from labeled GCs of single projections in vivo. Using this approach on the developing callosal projection of the mouse cerebral cortex, we mapped molecular enrichments in trans-hemispheric GCs relative to their parent cell bodies, producing paired subcellular proteomes and transcriptomes from single neuron subtypes directly from the brain. These data provide generalizable proof-of-principle for this approach, and reveal novel GC molecular specializations, including accumulations of the growth-regulating kinase mTOR2, together withmRNAs containing mTOR-dependent motifs3,4. These findings illuminate therelationships of RNA and protein subcellular distributions in developing projectionneurons, and provide a new systems-level approach for discovery of subtype- and stage-specific molecular substrates of circuit wiring, miswiring, and potential for regeneration.