Human and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions and even causes mental dysfunctions such as depression and anxiety disorders. In this article, we conducted a multimodal study cross-sectionally and longitudinally, to evaluate how neuropathic pain affects the brain. Using the spared nerve injury (SNI) model which promotes long-lasting mechanical allodynia, results showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network 2 weeks after injury. There are significant changes in the activity of the left thalamus (Th\_L) and left olfactory bulb (OB\_L) brain regions after SNI, as evidenced by both the blood oxygen level-dependent (BOLD) signal and c-Fos expression. Importantly, these changes were closely related to mechanical pain behavior of rats. However, it is worth noting that after morphine administration for analgesia, only the increased activity in the TH region is re...

Dopamine neurons switch from tonic pacemaker activity to high-frequency bursts in response to salient stimuli. These bursts lead to superlinear increases in dopamine release, and the degree of this increase is highly dependent on firing frequency. The superlinearity and frequency dependence of dopamine release implicate short-term plasticity processes. The presynaptic Ca2+-sensor synaptotagmin-7 (SYT7) has suitable properties to mediate such short-term plasticity and has been implicated in regulating dopamine release from somatodendritic compartments. Here, we use a genetically encoded dopamine sensor and whole-cell electrophysiology in Syt7 KO mice to determine how SYT7 contributes to both axonal and somatodendritic dopamine release. We find that SYT7 mediates a hidden component of facilitation of release from dopamine terminals that can be unmasked by lowering initial release probability or by predepressing synapses with low-frequency stimulation. Depletion of SYT7 increased short-term depression and red...

Sleep and muscle injury-related pain are in negative relationship, and sleep extension may be a favorable countermeasure. In response to muscle injury, an adaptive sleep response has been described in rats, characterized by an increase in total sleep time (TST) and nonrapid eye movement (NREM) sleep. This study examined the effects of photoperiod lengthening (a model of sleep prolongation in rats) on the sleep characteristics of muscle-injured rats and whether this lengthening could benefit injury-induced mechanical hyperalgesia using the Von Frey test. Switching from the conventional 12:12 light/dark (LD) photoperiod (light on: 08:00–20:00) to LD 16:8 (light extended to 24:00) gives rats an extra window of sleep. Our results show higher TST and NREM sleep times in LD 16:8 versus LD 12:12 injured rats during 4 h of light lengthening for 7 d postinjury, showing the efficiency of photoperiod lengthening to increase sleep time in injured rats. In addition, a cumulative effect with the adaptive sleep response ...

The subependymal zone (SEZ), also known as the subventricular zone (SVZ), constitutes a neurogenic niche that persists during postnatal life. In humans, the neurogenic potential of the SEZ declines after the first year of life. However, studies discovering markers of stem and progenitor cells highlight the neurogenic capacity of progenitors in the adult human SEZ, with increased neurogenic activity occurring under pathological conditions. In the present study, the complete cellular niche of the adult human SEZ was characterized by single-nucleus RNA sequencing, and compared between four youth (age 16–22) and four middle-aged adults (age 44–53). We identified 11 cellular clusters including clusters expressing marker genes for neural stem cells (NSCs), neuroblasts, immature neurons, and oligodendrocyte progenitor cells. The relative abundance of NSC and neuroblast clusters did not differ between the two age groups, indicating that the pool of SEZ NSCs does not decline in this age range. The relative abundanc...

In the field of behavioral neuroscience, the classification and scoring of animal behavior play pivotal roles in the quantification and interpretation of complex behaviors displayed by animals. Traditional methods have relied on video examination by investigators, which is labor-intensive and susceptible to bias. To address these challenges, research efforts have focused on computational methods and image-processing algorithms for automated behavioral classification. Two primary approaches have emerged: marker- and markerless-based tracking systems. In this study, we showcase the utility of “Augmented Reality University of Cordoba” (ArUco) markers as a marker-based tracking approach for assessing rat engagement during a nose-poking go/no-go behavioral task. In addition, we introduce a two-state engagement model based on ArUco marker tracking data that can be analyzed with a rectangular kernel convolution to identify critical transition points between states of engagement and distraction. In this study, we ...

The cortical visual area, V4, has been considered to code contours that contribute to the intermediate-level representation of objects. The neural responses to the complex contour features intrinsic to natural contours are expected to clarify the essence of the representation. To approach the cortical coding of natural contours, we investigated the simultaneous coding of multiple contour features in monkey ( Macaca fuscata ) V4 neurons and their population-level representation. A substantial number of neurons showed significant tuning for two or more features such as curvature and closure, indicating that a substantial number of V4 neurons simultaneously code multiple contour features. A large portion of the neurons responded vigorously to acutely curved contours that surrounded the center of classical receptive field, suggesting that V4 neurons tend to code prominent features of object contours. The analysis of mutual information (MI) between the neural responses and each contour feature showed that most ...

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate ( Macaca mulatta ) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These “V1-bypassing” projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extr...

Daylight vision is mediated by cone photoreceptors in vertebrates, which synapse with bipolar cells (BCs) and horizontal (HCs) cells. This cone synapse is functionally and anatomically complex, connecting to eight types of depolarizing BCs (DBCs) and five types of hyperpolarizing BCs (HBCs) in mice. The dendrites of DBCs and HCs cells make invaginating ribbon synapses with the cone axon terminal, while HBCs form flat synapses with the cone pedicles. The molecular architecture that underpins this organization is relatively poorly understood. To identify new proteins involved in synapse formation and function we used an unbiased proteomic approach and identified LRFN2 (leucine-rich repeat and fibronectin III domain-containing 2) as a component of the DBC signaling complex. LRFN2 is selectively expressed at cone terminals and colocalizes with PNA, and other DBC signalplex members. In LRFN2 deficient mice, the synaptic markers: LRIT3, ELFN2, mGluR6, TRPM1 and GPR179 are properly localized. Similarly, LRFN2 exp...

The preBötzinger complex (preBötC), located in the medulla, is the essential rhythm-generating neural network for breathing. The actions of opioids on this network impair its ability to generate robust, rhythmic output, contributing to life-threatening opioid-induced respiratory depression (OIRD). The occurrence of OIRD varies across individuals and internal and external states, increasing the risk of opioid use, yet the mechanisms of this variability are largely unknown. In this study, we utilize a computational model of the preBötC to perform several in silico experiments exploring how differences in network topology and the intrinsic properties of preBötC neurons influence the sensitivity of the network rhythm to opioids. We find that rhythms produced by preBötC networks in silico exhibit variable responses to simulated opioids, similar to the preBötC network in vitro. This variability is primarily due to random differences in network topology and can be manipulated by imposed changes in network connect...

Neuroprotection after injury or in neurodegenerative disease remains a major goal for basic and translational neuroscience. Retinal ganglion cells (RGCs), the projection neurons of the eye, degenerate in optic neuropathies after axon injury, and there are no clinical therapies to prevent their loss or restore their connectivity to targets in the brain. Here we demonstrate a profound neuroprotective effect of the exogenous expression of various Ca2+/calmodulin-dependent protein kinase II (CaMKII) isoforms in mice. A dramatic increase in RGC survival following the optic nerve trauma was elicited by the expression of constitutively active variants of multiple CaMKII isoforms in RGCs using adeno-associated viral (AAV) vectors across a 100-fold range of AAV dosing in vivo. Despite this neuroprotection, however, short-distance RGC axon sprouting was suppressed by CaMKII, and long-distance axon regeneration elicited by several pro-axon growth treatments was likewise inhibited even as CaMKII further enhanced RGC s...