Selective visual attention allows the brain to focus on behaviorally relevant information while ignoring irrelevant signals. As a possible mechanism, routing-by-synchronization was proposed: neural populations receiving attended signals align their gamma-rhythmic activity to that of the sending populations, such that incoming spikes arrive at excitability peaks of receiving populations, enhancing signal transfer. Conversely, non-attended signals arrive unaligned to the receiver's oscillation, reducing signal transfer. Therefore, visual signals should be transferred through gamma-rhythmic bursts of information, resulting in a modulation of the stimulus content within the receiving population's activity by its gamma phase and amplitude. To test this prediction, we quantified gamma-phase-dependent stimulus content within neural activity from area V4 of two male macaques performing a visual attention task. For the attended stimulus, we find highest stimulus information content near excitability peaks, an effec...

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. Sarah Ackerman Chinnakkaruppan Adaikkan Anisha Adke Kadidia Adula Jayne Aiken Lucas

d-serine is the primary NMDAR coagonist at mature forebrain synapses and is synthesized by the enzyme serine racemase (SR). However, our understanding of the mechanisms regulating the availability of synaptic d-serine remains limited. Though early studies suggested d-serine is synthesized and released from astrocytes, more recent studies have demonstrated a predominantly neuronal localization of SR. More specifically, recent work intriguingly suggests that SR may be found at the postsynaptic density, yet the functional implications of postsynaptic SR on synaptic transmission are not yet known. Here, we show an age-dependent dendritic and postsynaptic localization of SR and d-serine by immunohistochemistry and electron microscopy in mouse CA1 pyramidal neurons. In addition, using a single-neuron genetic approach in SR conditional KO mice from both sexes, we demonstrate a cell-autonomous role for SR in regulating synaptic NMDAR function at Schaffer collateral (CA3)-CA1 synapses. Importantly, single-neuron ge...

Itch can be induced by activation of small-diameter DRG neurons, which express abundant intracellular fibroblast growth factor 13 (FGF13). Although FGF13 is revealed to be essential for heat nociception, its role in mediating itch remains to be investigated. Here, we reported that loss of FGF13 in mouse DRG neurons impaired the histamine-induced scratching behavior. Calcium imaging showed that the percentage of histamine-responsive DRG neurons was largely decreased in FGF13-deficient mice; and consistently, electrophysiological recording exhibited that histamine failed to evoke action potential firing in most DRG neurons from these mice. Given that the reduced histamine-evoked neuronal response was caused by knockdown of FGF13 but not by FGF13A deficiency, FGF13B was supposed to mediate this process. Furthermore, overexpression of histamine Type 1 receptor H1R, but not H2R, H3R, nor H4R, increased the percentage of histamine-responsive DRG neurons, and the scratching behavior in FGF13-deficient mice was hi...

Long-term memory (LTM) formation is a critical survival process by which an animal retains information about prior experiences in order to guide future behavior. In the experimentally advantageous marine mollusk Aplysia , LTM for sensitization can be induced by the presentation of two aversive shocks to the animal’s tail. Each of these training trials recruits distinct growth factor signaling systems that promote LTM formation. Specifically, whereas intact TrkB signaling during Trial 1 promotes an initial and transient increase of the immediate early gene apc/ebp mRNA, a prolonged increase in apc/ebp gene expression required for LTM formation requires the addition of TGFβ signaling during Trial 2. Here we explored the molecular mechanisms by which Trial 2 achieves the essential prolonged gene expression of apc/ebp . We find that this prolonged gene expression is not dependent on de novo transcription, but that apc/ebp mRNA synthesized by Trial 1 is post-transcriptionally stabilized by interacting with the ...

Triggering receptor expressed on myeloid cells 2 (TREM2), a receptor exclusively expressed by microglia in the brain, modulates microglial immune homeostasis. Human genetic studies have shown that the loss-of-function mutations in TREM2 signaling are strongly associated with an elevated risk of age-related neurodegenerative diseases including Alzheimer's disease (AD). Numerous studies have investigated the impact of TREM2 deficiency in the pathogenic process of AD. However, the role of TREM2 in shaping neuronal and cognitive function during normal aging is underexplored. In the present study, we employed behavioral, electrophysiological, and biochemical approaches to assess cognitive and synaptic function in male and female young and aged TREM2-deficient ( Trem2 −/−) mice compared with age-matched, sex-matched, and genetic background-matched wild-type (WT) C57BL/6J controls. Young Trem2 −/− mice exhibited normal cognitive function and synaptic plasticity but had increased dendritic spine density compared w...

Expression of the 17β-estradiol (E2) synthesis enzyme aromatase is highly upregulated in astrocytes following brain injury. However, the precise role of astrocyte-derived E2 in the injured brain remains unclear. In the current study, we generated a glial fibrillary acidic protein (GFAP) promoter-driven aromatase knock-out (GFAP-ARO-KO) mouse model to deplete astrocyte-derived E2 in the brain and determine its roles after global cerebral ischemia (GCI) in male and female mice. GFAP-ARO-KO mice were viable and fertile, with normal gross brain structure, normal morphology, intensity and distribution of astrocytes, normal aromatase expression in neurons, and normal cognitive function basally. In contrast, after GCI, GFAP-ARO-KO mice: (1) lacked the normal elevation of astrocyte aromatase and hippocampal E2 levels; (2) had significantly attenuated reactive astrogliosis; and (3) displayed enhanced neuronal damage, microglia activation, and cognitive deficits. RNA-sequencing (RNA-seq) analysis revealed that the i...

Single-cell analysis is revealing increasing diversity in gene expression profiles among brain cells. Traditional promotor-based viral gene expression techniques, however, cannot capture the growing variety among single cells. We demonstrate a novel viral gene expression strategy to target cells with specific miRNA expression using miRNA-guided neuron tags (mAGNET). We designed mAGNET viral vectors containing a CaMKIIα promoter and microRNA-128 (miR-128) binding sites, and labeled CaMKIIα+ cells with naturally low expression of miR-128 (Lm128C cells) in male and female mice. Although CaMKIIα has traditionally been considered as an excitatory neuron marker, our single-cell sequencing results reveal that Lm128C cells are CaMKIIα+ inhibitory neurons of parvalbumin or somatostatin subtypes. Further evaluation of the physiological properties of Lm128C cell in brain slices showed that Lm128C cells exhibit elevated membrane excitability, with biophysical properties closely resembling those of fast-spiking interne...

Functional specialization and plasticity are fundamental organizing principles of the brain. Since the mid-1800s, certain cognitive functions have been known to be lateralized, but the provenance and flexibility of hemispheric specialization remain open questions. Language is a uniquely human phenomenon that requires a delicate balance between neural specialization and plasticity, and language learning offers the perfect window to study these principles in the human brain. In the current study, we conducted two separate functional MRI experiments with language learners (male and female), one cross-sectional and one longitudinal, involving distinct populations and languages, and examined hemispheric lateralization and learning-dependent plasticity of the following three language systems: reading, speech comprehension, and verbal production. A multipronged analytic approach revealed a highly consistent pattern of results across the two experiments, showing (1) that in both native and non-native languages, wh...

Self-control allows humans the patience necessary to maximize reward attainment in the future. Yet it remains elusive when and how the preference to self-controlled choice is formed. We measured brain activity while female and male humans performed an intertemporal choice task in which they first received delayed real liquid rewards (forced-choice trial), and then made a choice between the reward options based on the experiences (free-choice trial). We found that, while subjects were awaiting an upcoming reward in the forced-choice trial, the anterior prefrontal cortex (aPFC) tracked a dynamic signal reflecting the pleasure of anticipating the future reward. Importantly, this prefrontal signal was specifically observed in self-controlled individuals, and moreover, interregional negative coupling between the prefrontal region and the ventral striatum (VS) became stronger in those individuals. During consumption of the liquid rewards, reduced ventral striatal activity predicted self-controlled choices in the...