Neurotoxic HIV-1 viral proteins contribute to the development of HIV-associated neurocognitive disorder (HAND), the prevalence of which remains high (30–50%) with no effective treatment available. Estrogen is a known neuroprotective agent; however, the diverse mechanisms of estrogen action on the different types of estrogen receptors is not completely understood. In this study, we determined the extent to which and mechanisms by which 17α-estradiol (17αE2), a natural less-feminizing estrogen, offers neuroprotection against HIV-1 gp120-induced neuronal injury. Endolysosomes are important for neuronal function, and endolysosomal dysfunction contributes to HAND and other neurodegenerative disorders. In hippocampal neurons, estrogen receptor α (ERα) is localized to endolysosomes and 17αE2 acidifies endolysosomes. ERα knockdown or overexpressing an ERα mutant that is deficient in endolysosome localization prevents 17αE2-induced endolysosome acidification. Furthermore, 17αE2-induced increases in dendritic spine ...

The primary somatosensory cortex (S1) plays a critical role in processing multiple somatosensations, but the mechanism underlying the representation of different submodalities of somatosensation in S1 remains unclear. Using in vivo two-photon calcium imaging that simultaneously monitors hundreds of layer 2/3 pyramidal S1 neurons of awake male mice, we examined neuronal responses triggered by mechanical, thermal, or pruritic stimuli. We found that mechanical, thermal, and pruritic stimuli activated largely overlapping neuronal populations in the same somatotopic S1 subregion. Population decoding analysis revealed that the local neuronal population in S1 encoded sufficient information to distinguish different somatosensory submodalities. Although multimodal S1 neurons responding to multiple types of stimuli exhibited no spatial clustering, S1 neurons preferring mechanical and thermal stimuli tended to show local clustering. These findings demonstrated the coding scheme of different submodalities of somatosen...

Space-specific neurons in the owl's midbrain form a neural map of auditory space, which supports sound-orienting behavior. Previous work proposed that a population vector (PV) readout of this map, implementing statistical inference, predicts the owl's sound localization behavior. This model also predicts the frontal localization bias normally observed and how sound-localizing behavior changes when the signal-to-noise ratio varies, based on the spread of activity across the map. However, the actual distribution of population activity and whether this pattern is consistent with premises of the PV readout model on a trial-by-trial basis remains unknown. To answer these questions, we investigated whether the population response profile across the midbrain map in the optic tectum of the barn owl matches these predictions using in vivo multielectrode array recordings. We found that response profiles of recorded subpopulations are sufficient for estimating the stimulus interaural time difference using responses f...

The editors depend heavily on outside reviewers in forming opinions about papers submitted to JNeurosci and would like to formally thank the following individuals for their help during the past year. Gloster B. Aaron Nobuhito Abe Aman Aberra Jose Francisco Abisambra Alfonso Abizaid Karina P.

Invited reviewers are asked to identify colleagues who assisted with review. JNeurosci would like to acknowledge the hard work of these collaborating reviewers and thank them for their service to the journal. Andrin Abegg Julia Abitbol Tobias Ackels Elie Adam Kadidia Adula Blanca Aldana Mor

In the article “Reducing Amyloid-Related Alzheimer's Disease Pathogenesis by a Small Molecule Targeting Filamin A,” by Hoau-Yan Wang, Kalindi Bakshi, Maya Frankfurt, Andres Stucky, Marissa Goberdhan, Sanket M. Shah, and Lindsay H. Burns, which appeared on pages [9773–9784][1] of the July 18,

The dorsal anterior cingulate cortex (dACC) plays a critical role in cognitive control over different domains of tasks. The dACC activities uniformly represent task-generic intensities of control signals across different tasks. However, it remains unclear whether the dACC activities could also encode task identities of control signals across different tasks. If so, how the two types of control information are coherently organized in the dACC? Decision uncertainty is an internally-generated control signal by retrospective monitoring, namely, metacognition, even with no external feedback. We here investigated neural representations of decision uncertainty accompanying three decision-making tasks in the domains of perception, rule-based inference, and memory using trial-by-trial univariate and multivariate analyses on functional magnetic imaging data acquired on human male and female healthy subjects. Our results demonstrated that the dACC represented decision uncertainty commonly across the three decision-ma...

Stable neural function requires an energy supply that can meet the intense episodic power demands of neuronal activity. Neurons have presumably optimized the volume of their bioenergetic machinery to ensure these power demands are met, but the relationship between presynaptic power demands and the volume available to the bioenergetic machinery has never been quantified. Here we estimated the power demands of six motor nerve terminals in female Drosophila larvae through direct measurements of neurotransmitter release and Ca2+ entry, and via theoretical estimates of Na+ entry and power demands at rest. Electron microscopy revealed that terminals with the highest power demands contained the greatest volume of mitochondria, indicating that mitochondria are allocated according to presynaptic power demands. In addition, terminals with the greatest power demand-to-volume ratio (∼66 nmol·min−1·μL−1) harbor the largest mitochondria packed at the greatest density. If we assume sequential and complete oxidation of gl...

Group I metabotropic glutamate receptors (mGluRs) have diverse functions in some fundamental neuronal processes, including modulation of synaptic plasticity and dysregulation of these receptors could lead to various neuropsychiatric disorders. Trafficking of group I mGluRs plays critical roles in controlling the precise spatio-temporal localization and activity of these receptors, both of which contribute to proper downstream signaling. Using “molecular replacement” approach in hippocampal neurons derived from mice of both sexes, we demonstrate a critical role for the post-synaptic density protein Norbin in regulating the ligand-induced internalization of group I mGluRs. We show that Norbin associates with protein kinase A (PKA) through its N-terminus and anchors mGluR5 through its C-terminus, both of which are necessary for the ligand-mediated endocytosis of mGluR5, a member of the group I mGluR family. A point mutation (A687G) at the C-terminus of Norbin inhibits the binding of Norbin to mGluR5 and block...

The Reuniens Nucleus (RE) is situated at the most ventral position of the midline thalamus. In rats and mice RE is distinguished by bidirectional connections with the hippocampus and medial prefrontal cortex (mPFC) and a role in memory and cognition. In primates, many foundational questions pertaining to RE remain unresolved. We addressed these issues by investigating the composition of the rhesus monkey RE in both sexes by labeling for gamma-aminobutyric acid (GABA), a marker of inhibitory neurons, and for the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR), which label thalamic excitatory neurons that project to cortex. As in rats and mice, the macaque RE was mostly populated by CB and CR neurons, characteristic of matrix-dominant nuclei, and had bidirectional connections with hippocampus and mPFC area 25 (A25). Unlike rodents, we found GABAergic neurons in the monkey RE, and a sparser but consistent population of core-associated thalamocortical PV neurons. RE had stronger ...