Texture is an important visual attribute for surface pattern discrimination and therefore object segmentation, but the neural bases of texture perception are largely unknown. Previously, we demonstrated that the responses of V4 neurons to naturalistic texture patches are sensitive to four key features of human texture perception: coarseness, directionality, regularity, and contrast. To begin to understand how distinct texture perception emerges from the dynamics of neuronal responses, in 2 macaque monkeys (1 male, 1 female), we investigated the relative contribution of the four texture attributes to V4 responses in terms of the strength and timing of response modulation. We found that the different feature dimensions are associated with different temporal dynamics. Specifically, the response modulation associated with directionality and regularity was significantly delayed relative to that associated with coarseness and contrast, suggesting that the latter are fundamentally simpler feature dimensions. The ...

Proprioception, the sense of limb and body position, generates a map of the body that is essential for proper motor control, yet we know little about precisely how neurons in proprioceptive pathways are wired. Defining the anatomy of secondary neurons in the spinal cord that integrate and relay proprioceptive and potentially cutaneous information from the periphery to the cerebellum is fundamental to understanding how proprioceptive circuits function. Here, we define the unique anatomical trajectories of long-range direct and indirect spinocerebellar pathways as well as local intersegmental spinal circuits using genetic tools in both male and female mice. We find that Clarke’s column (CC) neurons, a major contributor to the direct spinocerebellar pathway, has mossy fiber terminals that diversify extensively in the cerebellar cortex with axons terminating bilaterally, but with no significant axon collaterals within the spinal cord, medulla, or cerebellar nuclei. By contrast, we find that two of the indirect...

Spreading depolarizations (SDs) of gray matter occur in the brain, in different pathological conditions, and cause varying degrees of tissue damage depending on the extent of metabolic burden on the tissue. As might be expected for such large depolarizations, neurons exhibit bursts of action potentials as the wave propagates. However, the specific role of action potentials in SD propagation is unclear. This is potentially consequential, since sodium channel modulation has not been considered as a therapeutic target for SD-associated disorders, due to ambiguous experimental evidence. Using whole-cell electrophysiology and single-photon imaging in acute cortical slices from male C57Bl6 mice, we tested the effects of action potential blockade on SDs generated by two widely used induction paradigms. We found that action potential blockade using tetrodotoxin (TTX) restricted propagation of focally induced SDs, and significantly reduced the amplitude of neuronal depolarization, as well as its Ca2+ load. TTX also...

The binaural interaction component (BIC) is a sound-evoked electrophysiological signature of binaural processing in the auditory brainstem that has received attention as a potential biomarker for spatial hearing deficits. Yet the number of trials necessary to evoke the BIC, or its measurability, seems to vary across species: while it is easily measured in small rodents, it has proven to be highly variable and less reliably measured in humans. This has hindered its potential use as a diagnostic tool. Further measurements of the BIC across a wide range of species could help us better understand its origin and the possible reasons for the variation in its measurability. Statistical analysis on the function relating BIC DN1 amplitude and the interaural time difference has been performed in only a few small rodent species, thus is remains to be shown how the results apply to more taxonomically diverse mammals, and those with larger heads. To fill this gap we measured BICs in Rhesus Macaque. We show the overall ...

Angelman syndrome (AS) is a neurodevelopmental disorder with unique behavioral phenotypes, seizures, and distinctive electroencephalographic (EEG) patterns. Recent studies identified motor, social communication, and learning and memory deficits in a CRISPR engineered rat model with a complete maternal deletion of the Ube3a gene. It is unknown whether this model recapitulates other aspects of the clinical disorder. We report here the effect of Ube3a maternal deletion in the rat on epileptiform activity, seizure threshold, and quantitative EEG. Using video-EEG monitoring, we assessed spectral power and epileptiform activity early postnatally through adulthood. While EEG power was similar to wildtype (WT) at 1.5 weeks postnatally, at all other ages analyzed, our findings were similar to the AS phenotype in mice and humans with significantly increased delta power. Analysis of epileptiform activity in juvenile and adult rats showed increased time spent in epileptiform activity in AS compared to WT rats. We eval...

We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a significant increase in the number of detected hypocretin/orexin (Hcrt) producing neurons. However it remains unknown how this increase affects target areas of the hypocretin system involved in opioid withdrawal, including the locus coeruleus (LC) and the A1/A2 medullary regions. Using a combination of immunohistochemical, biochemical, imaging, and behavioral techniques we now show that the increase in detected hypocretin cell number translates into a significant increase in hypocretin innervation and tyrosine hydroxylase (TH) levels in the LC without affecting norepinephrine (NE) containing neuronal cell number. We show that the increase in TH is completely dependent in Hcrt innervation. The A1/A2 regions were unaffected by morphine treatment. Manipulation of the Hcrt system may affect opioid addiction and withdrawal. SIGNIFICANT STATEMENT Previously we have shown that the hypothalamic hypocretin system und...

Previous studies have shown that timing of sensory stimulation during the cardiac cycle interacts with perception. Given the natural coupling of respiration and cardiac activity, we investigated here their joint effects on tactile perception. Forty-one healthy female and male human participants reported conscious perception of finger near-threshold electrical pulses (33% null trials) and decision confidence while electrocardiography, respiratory activity, and finger photoplethysmography were recorded. Participants adapted their respiratory cycle to expected stimulus onsets to preferentially occur during late inspiration/early expiration. This closely matched heart rate variation (sinus arrhythmia) across the respiratory cycle such that most frequent stimulation onsets occurred during the period of highest heart rate probably indicating highest alertness and cortical excitability. Tactile detection rate was highest during the first quadrant after expiration onset. Inter-individually, stronger respiratory ph...

In the article “Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore,” by Sebastian A. Barrientos, Nicolas W. Martinez, Soonmoon Yoo, Juan S. Jara, Sebastian Zamorano, Claudio Hetz, Jeffery L. Twiss, Jaime Alvarez, and Felipe A. Court, which appeared on pages [966–

Human epidemiological studies implicate exposure to infection during gestation in the etiology of neurodevelopmental disorders. Animal models of maternal immune activation (MIA) have identified the maternal immune response as the critical link between maternal infection and aberrant offspring brain and behavior development. Here we evaluate neurodevelopment of male rhesus monkeys ( Macaca mulatta ) born to MIA-treated dams ( n = 14) injected with a modified form of the viral mimic polyinosinic:polycytidylic acid at the end of the first trimester. Control dams received saline injections at the same gestational time points ( n = 10) or were untreated ( n = 4). MIA-treated dams exhibited a strong immune response as indexed by transient increases in sickness behavior, temperature, and inflammatory cytokines. Although offspring born to control or MIA-treated dams did not differ on measures of physical growth and early developmental milestones, the MIA-treated animals exhibited subtle changes in cognitive develo...