Epigenetic mechanisms, such as histone modifications, regulate responsiveness to drugs of abuse, such as cocaine, but relatively little is known about the regulation of addictive-like behaviors by DNA methylation. To investigate the influence of DNA methylation on the locomotor-activating effects of cocaine and on drug-seeking behavior, rats receiving methyl supplementation via chronic l-methionine (MET) underwent either a sensitization regimen of intermittent cocaine injections or intravenous self-administration of cocaine, followed by cue-induced and drug-primed reinstatement. MET blocked sensitization to the locomotor-activating effects of cocaine and attenuated drug-primed reinstatement, with no effect on cue-induced reinstatement or sucrose self-administration and reinstatement. Furthermore, upregulation of DNA methyltransferase 3a and 3b and global DNA hypomethylation were observed in the nucleus accumbens core (NAc), but not in the medial prefrontal cortex (mPFC), of cocaine-pretreated rats. Glutama...

Modern spatial navigation requires fluency with multiple representational formats, including visual scenes, signs, and words. These formats convey different information. Visual scenes are rich and specific but contain extraneous details. Arrows, as an example of signs, are schematic representations in which the extraneous details are eliminated, but analog spatial properties are preserved. Words eliminate all spatial information and convey spatial directions in a purely abstract form. How does the human brain compute spatial directions within and across these formats? To investigate this question, we conducted two experiments on men and women: a behavioral study that was preregistered and a neuroimaging study using multivoxel pattern analysis of fMRI data to uncover similarities and differences among representational formats. Participants in the behavioral study viewed spatial directions presented as images, schemas, or words (e.g., “left”), and responded to each trial, indicating whether the spatial direc...

Neuroscientists endeavor to unravel the mysteries of brain functions and dysfunctions. A common research strategy involves measuring specific parameters across various conditions. These measurements are then typically repeated, averaged, and used to infer general patterns or rules. The act of averaging data is an ancient practice; for instance, early astronomers in Babylonian, Chinese, and Indian cultures implicitly averaged observations of celestial phenomena to predict significant periods, such as those crucial for agriculture. Averaging is a sound approach when the process being studied follows to a mathematical function, represented as y = f(x), where f is a very general function. This is true even if the exact function is not known at the outset of the experiments. Implicit in this method is the assumption that any variations in measurements arise from imperfections in the recording process since a consistent mathematical rule suggests that identical inputs should always yield the same output. In ess...

The prefrontal cortex is made up of neocortical areas thought to mediate aspects of the temporal and spatial organization of behavior. One of the prime output targets of the prefrontal cortex is the striatum, which is thought to operate in series with the prefrontal cortex in some neural computations. We have analyzed this prefronto- striatal projection in cynomolgus monkeys by combining anterograde neuronal tract tracing methods with neurochemical markers for the striosome and matrix compartments of the striatum. Our results single out two parts of the frontal cortex as projecting densely to the striosome compartment of the striatum: the posterior orbitofrontal/anterior insular cortex and the mediofrontal prelimbic/anterior cingulate cortex. These areas jointly innervated striosomes in the anterior and ventromedial striatum, mainly in the caudate nucleus. Striosomes in the dorsolateral striatum were never labeled. Thus, the anatomical subsystem defined by striosome affiliation includes three cortical and ...

Chronic low-grade inflammation and stress exposure are key contributing factors in the etiology and progression of many neuropsychiatric disorders. Dietary emulsifiers are commonly added to processed foods and are classified by the Food and Drug Adminis...

Corticotropin-releasing factor-positive (CRF+) neurons in the paraventricular nucleus of the hypothalamus (PVN) drive activity of the hypothalamic-pituitary-adrenal (HPA) axis. The release of CRF from these cells initiates the neuroendocrine stress resp...

Cochlear implants (CIs) are auditory neuroprostheses that restore hearing to over 500,000 humans world-wide, including over 3,000 at our clinic at NYU since 1984. The CI restores hearing by bypassing damaged parts of the sensory transduction epithelium ...

Hippocampal networks are capable of maintaining synchronized bursting activity for prolonged periods. Yet, in vitro synaptic terminals undergo a rapid depletion of their readily releasable pool (RRP) of vesicles in response to short trains of stimuli. The rate at which neurons can re-prime vesicles provides an upper limit for the rate of sustained synaptic signaling. Here, we estimate this replenishment rate at individual synapses by measuring postsynaptic Ca2+ transients mediated by NMDA receptors during high frequency stimulation. We reasoned that at the onset of train stimulation, the Ca2+ indicator would saturate in response the release of the RRP. After this initial phase, Ca2+ levels would fall back to baseline and subsequent postsynaptic Ca2+ transients would only arise from release of newly primed vesicles, which would then be used to estimate the rates of recovery. To monitor activity at single CA1 neuron synapses in acute slices, we measure postsynaptic Ca2+ influx (in response to continuous 20-5...

The acoustic click evokes no peristimulus firing in individual primary afferents. Hypothetically, then, click level must be encoded in the synchronous burst of voltage spikes evoked across the entire eighth nerve (E.A. Radionova, Sov. Phys.-Acoust. 8, 1963, 350-355). It is impossible to count those spikes, but they do produce a measurable epiphenomenon, the N1 component of the peripheral compound action potential (CAP). Each spike contributes equally, so that N1 can be assumed proportional to spike count. If spike count is assumed to have a Gaussian distribution whose variance does not change over a just-detectable-change in level, the intensity-difference limen is given by Signal Detection Theory as follows: d-prime times the standard deviation of N1, divided by the rate-of-change of N1 with level. The term “N1” can be replaced by “loudness” if loudness is assumed proportional to spike count, and if a just-detectable-change in loudness is the change in percept corresponding to a just-detectable-change in ...

Substance abusers show impaired performance on cognitive tests of decision making that engage the orbitofrontal cortex (OFC). This study evaluated the impact of chronic cocaine self-administration on OFC function in rhesus monkeys, using a stimulus reversal task. Two control animals trained to respond for food, and two animals that had chronically self-administered both cocaine and cocaethylene in progressive ratio comparisons of reinforcing efficacy over a period of two years were tested. Mean cumulative intakes were: cocaine 285 mg/kg and cocaethylene 68 mg/kg. A touch screen monitor was used to present stimuli and record responses, using E-prime software. Animals were chair restrained and rewarded with water. They were acquainted with the apparatus by initially being rewarded for touching a stimulus on the screen. Upon proficiency at that task, the reversal task was begun. Bitmap images were presented to the left and right of the screen. Touching one resulted in a larger water reward (3X) than the other...