Repeated pairing of a drug with a neutral stimulus, such as a cue or context, leads to the attribution of the drug's reinforcing properties to that stimulus, and exposure to that stimulus in the absence of the drug can elicit drug-seeking. A principal role for the NAc in the response to drug-associated stimuli has been well documented. Direct and indirect pathway medium spiny neurons (dMSNs and iMSNs) have been shown to bidirectionally regulate cue-induced heroin-seeking in rats expressing addiction-like phenotypes, and a shift in NAc activity toward the direct pathway has been shown in mice following cocaine conditioned place preference (CPP). However, how NAc signaling guides heroin CPP, and whether heroin alters the balance of signaling between dMSNs and iMSNs, remains unknown. Moreover, the role of NAc dopamine signaling in heroin reinforcement is unclear. Here, we integrate fiber photometry for in vivo monitoring of dopamine and dMSN/iMSN calcium activity with a heroin CPP procedure in rats to begin t...

Functional hemispheric lateralization is a basic principle of brain organization. In the auditory domain, the right auditory cortex (AC) determines the pitch direction of continuous auditory stimuli whereas the left AC discriminates gaps in these stimuli. The involved functional interactions between the two sides, mediated by commissural connections, are poorly understood. Here, we selectively disrupted the interhemispheric cross talk from the left to the right primary AC and vice versa using chromophore-targeted laser-induced apoptosis of the respective projection neurons, which make up 6–17% of all AC neurons in Layers III, V, and VI. Following photolysis, male gerbils were trained in a first experimental set to discriminate between rising and falling frequency-modulated (FM) tone sweeps. The acquisition of the task was significantly delayed in lesioned animals of either lesion direction. However, the final discrimination performance and hit rate was lowest for animals with left-side lesioned commissural...

Motor skills learned through practice are consolidated at later time, which can include nighttime, but the time course of motor memory consolidation and its underlying mechanisms remain poorly understood. We investigated neural substrates underlying motor memory consolidation of learned changes in birdsong, a tractable model system for studying neural basis of motor skill learning. Previous studies in male zebra finches and Bengalese finches have demonstrated that adaptive changes in adult song structure learned through a reinforcement paradigm are initially driven by a cortical-basal ganglia circuit, and subsequently consolidated into downstream cortical motor circuitry. However, the time course of the consolidation process, including whether it occurs offline during nighttime or online during daytime, remains unclear and even controversial. Here, we provide in both species experimental evidence of virtually no consolidation of learned vocal changes during nighttime. We demonstrate instead that the consol...

Candler Paige, Isabel Plasencia-Fernandez, Moeno Kume, Melina Papalampropoulou-Tsiridou, Louis-Etienne Lorenzo, et al. (see pages [1930–1944][1]) The molecular and cellular mechanisms of pain are somewhat different in males and females. In rodents, for example, spinal microglia are required for

Extensive training can improve performance on almost every visual task, through a process called visual perceptual learning ([He et al., 2021][1]). Visual perceptual learning has been applied to rehabilitate impaired vision for patients with low vision ([He et al., 2021][1]). In addition, visual

The superficial dorsal horn (SDH) of the spinal cord represents the first site of integration between innocuous and noxious somatosensory stimuli. According to gate control theory, diverse populations of excitatory and inhibitory interneurons within the SDH are activated by distinct sensory afferents, and their interplay determines the net nociceptive output projecting to higher pain centers. Although specific SDH cell types are ill defined, numerous classifications schemes find that excitatory and inhibitory neurons fundamentally differ in their morphology, electrophysiology, neuropeptides, and pain-associated plasticity; yet little is known about how these neurons respond over a range of natural innocuous and noxious stimuli. To address this question, we applied an in vivo imaging approach in male mice where the genetically encoded calcium indicator GCaMP6s was expressed either in vGluT2-positive excitatory or vIAAT-positive inhibitory neurons. We found that inhibitory neurons were markedly more sensitiv...

Single hippocampal cells encode the spatial position of an animal by increasing their firing rates within “place fields”, and by shifting the phase of their spikes to earlier phases of the ongoing theta oscillations (theta phase precession). Whether other forms of spatial phase changes exist in the hippocampus is unknown. Here, we used high-density electrophysiological recordings in mice of either sex running back and forth on a 150 cm linear track. We found that the instantaneous phase of spikes shifts to progressively later theta phases as the animal traverses the place field. We term this shift theta “phase rolling”. Phase rolling is opposite in direction to precession, faster than precession, and occurs between distinct theta cycles. Place fields that exhibit phase rolling are larger than non-rolling fields, and in-field spikes occur in distinct theta phases in rolling compared to non-rolling fields. As a phase change associated with position, theta phase rolling may be used to encode space. Significa...

The ability to recall something we encounter only once and unexpectedly—for example, that a food type is poisonous—is crucial for survival. Yet, neuroscientific research in recent decades has been dominated by incremental learning paradigms, relatively neglecting how the brain can learn

The medial temporal lobe (MTL) is connected to the rest of the brain through two main networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. Given the crucial role of the MTL and networks in the physiopathology of Alzheimer's disease (AD), the present study aimed at (1) investigating whether MTL atrophy propagates specifically within the AT and PM networks, and (2) evaluating the vulnerability of these networks to AD proteinopathies. To do that, we used neuroimaging data acquired in human male and female in three distinct cohorts: (1) resting-state functional MRI (rs-fMRI) from the aging brain cohort (ABC) to define the AT and PM networks ( n = 68); (2) longitudinal structural MRI from Alzheimer's disease neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns ( n = 349); and (3) positron emission tomography (PET) data from ADNI3 to evaluate the networks' vulnerability to amyloid and tau ( n = 186). Our results suggest that the atrophy of distinct MTL subregions ...