Human fMRI studies show that insulin influences brain activity in regions that mediate reward and motivation, including the nucleus accumbens (NAc). Insulin receptors are expressed by NAc medium spiny neurons (MSNs), and studies of cultured cortical and hippocampal neurons suggest that insulin influences excitatory transmission via presynaptic and postsynaptic mechanisms. However, nothing is known about how insulin influences excitatory transmission in the NAc. Furthermore, insulin dysregulation accompanying obesity is linked to cognitive decline, depression, anxiety, and altered motivation that rely on NAc excitatory transmission. Using whole-cell patch-clamp and biochemical approaches, we determined how insulin affects NAc glutamatergic transmission in nonobese and obese male rats and the underlying mechanisms. We find that there are concentration-dependent, bidirectional effects of insulin on excitatory transmission, with insulin receptor activation increasing and IGF receptor activation decreasing NAc ...

Metabotropic glutamate receptor 7 (mGlu7) is an inhibitory heterotrimeric G-protein-coupled receptor that modulates neurotransmitter release and synaptic plasticity at presynaptic terminals in the mammalian central nervous system. Recent studies have shown that rare mutations in glutamate receptors and synaptic scaffold proteins are associated with neurodevelopmental disorders (NDDs). However, the role of presynaptic mGlu7 in the pathogenesis of NDDs remains largely unknown. Recent whole-exome sequencing (WES) studies in families with NDDs have revealed that several missense mutations (c.1865G>A:p.R622Q; c.461T>C:p.I154T; c.1972C>T:p.R658W and c.2024C>A:p.T675K) or a nonsense mutation (c.1757G>A:p.W586X) in the GRM7 gene may be linked to NDDs. In the present study, we investigated the mechanistic links between GRM7 point mutations and NDD pathology. We find that the pathogenic GRM7 I154T and R658W/T675K mutations lead to the degradation of the mGlu7 protein. In particular, the GRM7 R658W/T675K mutation res...

We at Black In Neuro have led a grassroots effort to empower Black scholars in neuroscience-related fields in 2020. Author and activist Audre Lorde said, “Revolution is not a one-time event.” We call on our non-Black colleagues in neuroscience-related fields to mobilize and actively fight anti-

Jae-man Song, Minji Kang, Da-ha Park, Sunha Park, Sanghyeon Lee, et al. (see pages [2344–2359][1]) Metabotropic glutamate receptor 7 (mGluR7) is expressed throughout the brain, primarily in glutamatergic and GABAergic presynaptic terminals, where it inhibits neurotransmitter release. Mutations

The visual field region where a stimulus evokes a neural response is called the receptive field (RF). Analytical tools combined with functional MRI (fMRI) can estimate the RF of the population of neurons within a voxel. Circular population RF (pRF) methods accurately specify the central position of the pRF and provide some information about the spatial extent (diameter) of the RF. A number of investigators developed methods to further estimate the shape of the pRF, for example, whether the shape is more circular or elliptical. There is a report that there are many pRFs with highly elliptical pRFs in early visual cortex (V1–V3; [Silson et al., 2018][1]). Large aspect ratios (>2) are difficult to reconcile with the spatial scale of orientation columns or visual field map properties in early visual cortex. We started to replicate the experiments and found that the software used in the publication does not accurately estimate RF shape: it produces elliptical fits to circular ground-truth data. We analyzed an i...

Extinction learning suppresses conditioned reward responses and is thus fundamental to adapt to changing environmental demands and to control excessive reward seeking. The medial prefrontal cortex (mPFC) monitors and controls conditioned reward responses. Abrupt transitions in mPFC activity anticipate changes in conditioned responses to altered contingencies. It remains, however, unknown whether such transitions are driven by the extinction of old behavioral strategies or by the acquisition of new competing ones. Using in vivo multiple single-unit recordings of mPFC in male rats, we studied the relationship between single-unit and population dynamics during extinction learning, using alcohol as a positive reinforcer in an operant conditioning paradigm. To examine the fine temporal relation between neural activity and behavior, we developed a novel behavioral model that allowed us to identify the number, onset, and duration of extinction-learning episodes in the behavior of each animal. We found that single...

Transient receptor potential melastatin 3 (TRPM3) is a heat-activated ion channel in primary sensory neurons of the dorsal root ganglia (DRGs). Pharmacological and genetic studies implicated TRPM3 in various pain modalities, but TRPM3 inhibitors were not validated in TRPM3−/− mice. Here we tested two inhibitors of TRPM3 in male and female wild-type and TRPM3−/− mice in nerve injury-induced neuropathic pain. We found that intraperitoneal injection of either isosakuranetin or primidone reduced heat hypersensitivity induced by chronic constriction injury (CCI) of the sciatic nerve in wild-type, but not in TRPM3−/− mice. Primidone was also effective when injected locally in the hindpaw or intrathecally. Consistently, intrathecal injection of the TRPM3 agonist CIM0216 reduced paw withdrawal latency to radiant heat in wild-type, but not in TRPM3−/− mice. Intraperitoneal injection of 2 mg/kg, but not 0.5 mg/kg isosakuranetin, inhibited cold and mechanical hypersensitivity in CCI, both in wild-type and TRPM3−/− mi...

The dentate gyrus (DG) of the hippocampus is important for cognition and behavior. However, the circuits underlying these functions are unclear. DG mossy cells (MCs) are potentially important because of their excitatory synapses on the primary cell type, granule cells (GCs). However, MCs also activate GABAergic neurons, which inhibit GCs. We used viral delivery of designer receptors exclusively activated by designer drugs (DREADDs) in mice to implement a gain- and loss-of-function study of MCs in diverse behaviors. Using this approach, manipulations of MCs could bidirectionally regulate behavior. The results suggest that inhibiting MCs can reduce anxiety-like behavior and improve cognitive performance. However, not all cognitive or anxiety-related behaviors were influenced, suggesting specific roles of MCs in some, but not all, types of cognition and anxiety. Notably, several behaviors showed sex-specific effects, with females often showing more pronounced effects than the males. We also used the immediate...

Gravity is a pervasive environmental stimulus and accurate graviception is required for optimal spatial orientation and postural stability. The primary graviceptors are the vestibular organs, which include angular velocity (semicircular canals) and linear acceleration (otolith organs) sensors. Graviception is degraded in patients with vestibular damage, resulting in spatial misperception and imbalance. Since minimal therapy is available for these patients, substantial effort has focused on developing a vestibular prosthesis or implant (VI) that reproduces information normally provided by the canals (since reproducing otolith function is very challenging technically). Prior studies demonstrated that angular eye velocity responses could be driven by canal-VI mediated angular head velocity information, but it remains unknown if a canal-VI could improve spatial perception and posture since these behaviors require accurate estimates of angular head position in space relative to gravity . Here, we tested the hyp...