The endogenous opioid system plays a crucial role in stress-induced analgesia. Mu-opioid receptors (MORs), one of major opioid receptors, are expressed widely in sub-populations of cells throughout the central nervous system. However, the potential roles of MORs expressed in glutamatergic (MORGlut) and γ-aminobutyric acidergic (MORGABA) neurons in stress-induced analgesia remains unclear. By examining tail-flick latencies to noxious radiant heat of male mice, here we investigated the contributions of MORGABA and MORGlut to behavioral analgesia and activities of neurons projecting from periaqueductal gray (PAG) to rostral ventromedial medulla (RVM) induced by a range of time courses of forced swim exposure. The moderate but not transitory or prolonged swim exposure induced a MOR-dependent analgesia, although all of these three stresses enhanced β-endorphin (β-EP) release. Selective deletion of MORGABA but not MORGlut clearly attenuated analgesia and blocked the enhancement of activities of PAG-RVM neurons i...

The brain areas that mediate the formation of auditory threat memory and perceptual decisions remain uncertain to date. Candidates include the primary (A1) and secondary (A2) auditory cortex, the medial division of the medial geniculate body (MGm), amygdala, and the temporal association cortex (TeA). We used chemogenetic and optogenetic manipulations with in vivo and in vitro patch-clamp recordings to assess the roles of these brain regions in threat memory learning in female mice. We found that conditioned sound (CS) frequency-dependent plasticity resulted in the formation of auditory threat memory in the TeA. This neural correlated auditory threat memory depended on CS frequency information from A1 glutamatergic subthreshold monosynaptic inputs, CS lateral inhibition from A2 glutamatergic disynaptic inputs, and non-frequency-specific facilitation from MGm glutamatergic monosynaptic inputs. These results indicate that the A2 and MGm work together in an inhibitory-facilitative role. SIGNIFICANCE STATEMENT...

How do people limit awareness of unwanted memories? When such memories intrude, a control process engages the right DLPFC (rDLPFC) to inhibit hippocampal activity and stop retrieval. It remains unknown how the need for control is detected, and whether control operates proactively to prevent unwelcome memories from being retrieved, or responds reactively, to counteract intrusions. We hypothesized that dorsal ACC (dACC) detects the emergence of an unwanted trace in awareness and transmits the need for inhibitory control to rDLPFC. During a memory suppression task, we measured in humans (both sexes) trial-by-trial variations in the theta power and N2 amplitude of dACC, two EEG markers that are thought to reflect the need for control. With simultaneous EEG-fMRI recordings, we tracked interactions among dACC, rDLPFC, and hippocampus during suppression. We found a clear role of dACC in detecting the need for memory control and upregulating prefrontal inhibition. Importantly, we identified distinct early (300–450...

Signal integration of converging neural circuits is poorly understood. One example is in the retina where the integration of rod and cone signaling is responsible for the large dynamic range of vision. The relative contribution of rods versus cones is dictated by a complex function involving background light intensity and stimulus temporal frequency. One understudied mechanism involved in coordinating rod and cone signaling onto the shared retinal circuit is the hyperpolarization activated current ( I h) mediated by hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels expressed in rods and cones. I h opposes membrane hyperpolarization driven by activation of the phototransduction cascade and modulates the strength and kinetics of the photoreceptor voltage response. We examined conditional knock-out (KO) of HCN1 from mouse rods using electroretinography (ERG). In the absence of HCN1, rod responses are prolonged in dim light which altered the response to slow modulation of light intensity bo...

We used the chromatic visual evoked potential (cVEP) to study responses in human visual cortex evoked by equiluminant color stimuli for 6 male and 11 female observers. Large-area, colored squares were used to stimulate Single-Opponent cells preferentially, and fine color-checkerboard stimuli were used to activate Double-Opponent responses preferentially. Stimuli were modulated along the following two directions in color space: (1) the cardinal direction, L-M or M-L of DKL (Derrington, Krauskopf, and Lennie) space; and (2) the line from the white point to the color of the Red LED in the display screen, which was approximately intermediate between the L-M and -S directions in DKL space in cone-contrast coordinates. The amplitudes of cVEPs to large squares were smaller than those to checkerboards, and the latency of the cVEP response to squares was significantly less than the checkerboard latency. The latency of cVEP responses to the squares varied little with cone-contrast unlike the steep reduction of laten...

Colten K. Lankford, Yumiko Umino, Deepak Poria, Vladimir Kefalov, Eduardo Solessio, et al. (see pages [4231–4249][1]) The presence of two types of photoreceptors—rods and cones—in the retina allows animals to see over a broad range of light intensity. In faint light (scotopic conditions),

Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinson's disease). Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioral modulation. Interestingly, while a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences. The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. A total of 33 he...

The Protocadherin-10 ( PCDH10 ) gene is associated with autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD), and major depression (MD). The PCDH10 protein is a homophilic cell adhesion molecule that belongs to the δ2-protocadherin family. PCDH10 is highly expressed in the developing brain, especially in the basolateral nucleus of the amygdala (BLA). However, the role of PCDH10 in vivo has been debatable: one paper reported that a Pcdh10 mutant mouse line showed changes in axonal projections; however, another Pcdh10 mutant mouse line was reported to have failed to detect axonal phenotypes. Therefore, the actual roles of PCDH10 in the brain remain to be elucidated. We established a new Pcdh10 KO mouse line using the CRISPR/Cas9 system, without inserting gene cassettes to avoid nonspecific effects, examined the roles of PCDH10 in the brain, and studied the behavioral consequences of Pcdh10 inactivation. Here, we show that Pcdh10 KO mice do not show defects in axonal development. Instead, we fi...