Visual processing is segregated into ON and OFF channels as early as in the retina, and the superficial (output) layers of the primary visual cortex are dominated by neurons preferring dark stimuli. However, it is not clear how the timing of neural processing differs between “darks” and “brights” in general, especially in light of psychophysical evidence; it is also equally not clear how subcortical visual pathways that are critical for active orienting represent stimuli of positive (luminance increments) and negative (luminance decrements) contrast polarity. Here, we recorded from all visually-responsive neuron types in the superior colliculus (SC) of two male rhesus macaque monkeys. We presented a disc (0.51 deg radius) within the response fields (RF’s) of neurons, and we varied, across trials, stimulus Weber contrast relative to a gray background. We also varied contrast polarity. There was a large diversity of preferences for darks and brights across the population. However, regardless of individual ne...

Enteric glia are a unique population of peripheral neuroglia that regulate homeostasis in the enteric nervous system (ENS) and intestinal functions. Despite existing in functionally diverse regions of the gastrointestinal tract, enteric glia have been approached scientifically as a homogenous group of cells. This assumption is at odds with the functional specializations of gastrointestinal organs and recent data suggesting glial heterogeneity in the brain and ENS. Here, we used calcium imaging in transgenic mice of both sexes expressing genetically encoded calcium sensors in enteric glia and conducted contractility studies to investigate functional diversity among myenteric glia in two functionally distinct intestinal organs: the duodenum and the colon. Our data show that myenteric glia exhibit regionally distinct responses to neuromodulators that require intercellular communication with neurons to differing extents in the duodenum and colon. Glia regulate intestinal contractility in a region- and pathway-...

Intraneuronal chloride concentrations ([Cl−]i) decrease during development resulting in a shift from depolarizing to hyperpolarizing GABA responses via chloride-permeable GABAA receptors. This GABA shift plays a pivotal role in postnatal brain development, and can be strongly influenced by early life experience. Here, we assessed the applicability of the recently developed fluorescent SuperClomeleon (SClm) sensor to examine changes in [Cl−]i using two-photon microscopy in brain slices. We used SClm mice of both sexes to monitor the developmental decrease in neuronal chloride levels in organotypic hippocampal cultures. We could discern a clear reduction in [Cl−]i between day in vitro (DIV)3 and DIV9 (equivalent to the second postnatal week in vivo ) and a further decrease in some cells until DIV22. In addition, we assessed alterations in [Cl−]i in the medial prefrontal cortex (mPFC) of postnatal day (P)9 male SClm mouse pups after early life stress (ELS). ELS was induced by limiting nesting material between...

Manipulating the activity of ventral tegmental area (VTA) dopamine (DA) neurons can drive nocifensive reflexes, and their firing rates are reduced following noxious stimuli. However, the pain-relevant inputs to the VTA remain incompletely understood. In this study, we used male and female mice in combination with identified dopamine and GABA neurons in the VTA that receive excitatory inputs from the periaqueductal gray (PAG), a nexus of ascending pain information. We tested whether PAG–VTA synapses undergo functional plasticity in response to a pain model using optical stimulation in conjunction with slice electrophysiology. We found that acute carrageenan inflammation does not significantly affect the strength of excitatory PAG synapses onto VTA DA neurons. However, at the PAG synapses on VTA GABA neurons, the subunit composition of NMDA receptors is altered; the complement of NR2D subunits at synaptic sites appears to be lost. Thus, our data support a model in which injury initially alters synapses on VT...

Brain circuits are composed of diverse cell types with distinct morphologies, connections, and distributions of ion channels. Modeling suggests that the spatial distribution of the extracellular voltage during a spike depends on cellular morphology, connectivity, and identity. However, experimental evidence from the intact brain is lacking. Here, we combined high-density recordings from hippocampal region CA1 and neocortex of freely moving mice with optogenetic tagging of parvalbumin-immunoreactive (PV) cells. We used ground truth tagging of the recorded pyramidal cells (PYR) and PV cells to construct binary classification models. Features derived from single-channel waveforms or from spike timing alone allowed near-perfect classification of PYR and PV cells. To determine whether there is unique information in the spatial distribution of the extracellular potentials, we removed all single-channel waveform information from the multichannel waveforms using an event-based delta-transformation. We found that s...

Mitochondrial dysfunction is one of the basic hallmarks of cellular pathology in neurodegenerative diseases. Since the metabolic activity of neurons is highly dependent on energy supply, nerve cells are especially vulnerable to impaired mitochondrial function. Besides providing oxidative phosphorylation, mitochondria are also involved in controlling levels of second messengers such as Ca2+ ions and reactive oxygen species (ROS). Interestingly, the critical role of mitochondria as producers of ROS is closely related to P2XR purinergic receptors, the activity of which is modulated by free radicals. Here, we review the relationships between the purinergic signaling system and affected mitochondrial function. Purinergic signaling regulates numerous vital biological processes in the CNS. The two main purines, ATP and adenosine, act as excitatory and inhibitory neurotransmitters, respectively. Current evidence suggests that purinergic signaling best explains how neuronal activity is related to neuronal electrica...

Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN), which is then relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated injury leading to RGC axonal pathology, disruption of RGC outputs to the brain, and eventual apoptotic loss of RGC somata. The consequences of elevated IOP and glaucomatous pathology on RGC signaling to the dLGN are largely unknown yet are likely to contribute to vision loss. Here, we used anatomic and physiological approaches to study the structure and function of retinogeniculate (RG) synapses in male and female DBA/2J (D2) mice with inherited glaucoma before and after IOP elevation. D2 mice showed progressive loss of anterograde optic tract transport to the dLGN and vGlut2 labeling of RGC axon terminals while patch-clamp measurements of RG synaptic function showed that synaptic transmission was reduced in 9-m...

Visual accuracy is consistently shown to be modulated around the time of the action execution. The neural underpinning of this motor-induced modulation of visual perception is still unclear. Here, we investigate with EEG whether it is related to the readiness potential, an event-related potential (ERP) linked to motor preparation. Across 18 human participants, the magnitude of visual modulation following a voluntary button press was found to correlate with the readiness potential amplitude measured during visual discrimination. Participants’ amplitude of the readiness potential in a purely motor-task was also found to correlate with the extent of the motor-induced modulation of visual perception in the visuomotor task. These results provide strong evidence that perceptual changes close to action execution are associated with motor preparation processes and that this mechanism is independent of task contingencies. Further, our findings suggest that the readiness potential provides a fingerprint of individua...

When looking around a visual scene, humans make saccadic eye movements to fixate objects of interest. While the extraocular muscles can execute saccades in any direction, not all saccade directions are equally likely: saccades in horizontal and vertical directions are most prevalent. Here, we asked whether head orientation plays a role in determining saccade direction biases. Study participants ( n  = 14) viewed natural scenes and abstract fractals (radially symmetric patterns) through a virtual reality headset equipped with eye tracking. Participants’ heads were stabilized and tilted at −30°, 0°, or 30° while viewing the images, which could also be tilted by −30°, 0°, and 30° relative to the head. To determine whether the biases in saccade direction changed with head tilt, we calculated polar histograms of saccade directions and cross-correlated pairs of histograms to find the angular displacement resulting in the maximum correlation. During free viewing of fractals, saccade biases largely followed the or...

The oral cavity is exposed to a remarkable range of noxious and innocuous conditions, including temperature fluctuations, mechanical forces, inflammation, and environmental and endogenous chemicals. How such changes in the oral environment are sensed is not completely understood. Transient receptor potential (TRP) ion channels are a diverse family of molecular receptors that are activated by chemicals, temperature changes, and tissue damage. In non-neuronal cells, TRP channels play roles in inflammation, tissue development, and maintenance. In somatosensory neurons, TRP channels mediate nociception, thermosensation, and chemosensation. To assess whether TRP channels might be involved in environmental sensing in the human oral cavity, we investigated their distribution in human tongue and hard palate biopsies. TRPV3 and TRPV4 were expressed in epithelial cells with inverse expression patterns where they likely contribute to epithelial development and integrity. TRPA1 immunoreactivity was present in fibrobla...