The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure (POE); however, the long-term effects of POE on offspring behavior and neurodevelopment remain relatively unknown. The advantages and disadvantages of the various preclinical POE models developed over the last several decades are discussed in the context of clinical and translational relevance. Although considerable and important variability exists among preclinical models of POE, the examination of these preclinical models has revealed that opioid exposure during the prenatal period contributes to maladaptive behavioral development as offspring mature including an altered responsiveness to rewarding drugs and increased pain response. The present review summarizes key findings demonstrating the impact of POE on offspring drug self-administration (SA), drug consumption, the reinforcing properties of drugs, drug tolerance, and other reward-related behaviors such as hypersensitivity to pain. Potential unde...

Band ratio measures, computed as the ratio of power between two frequency bands, are a common analysis measure in neuroelectrophysiological recordings. Band ratio measures are typically interpreted as reflecting quantitative measures of periodic, or oscillatory, activity. This assumes that the measure reflects relative powers of distinct periodic components that are well captured by predefined frequency ranges. However, electrophysiological signals contain periodic components and a 1/f-like aperiodic component, the latter of which contributes power across all frequencies. Here, we investigate whether band ratio measures truly reflect oscillatory power differences, and/or to what extent ratios may instead reflect other periodic changes, such as in center frequency or bandwidth, and/or aperiodic activity. In simulation, we investigate how band ratio measures relate to changes in multiple spectral features, and show how multiple periodic and aperiodic features influence band ratio measures. We validate these ...

Cortical interneuron (CIN) dysfunction is thought to play a major role in neuropsychiatric conditions like epilepsy, schizophrenia and autism. It is therefore essential to understand how the development, physiology, and functions of CINs influence cortical circuit activity and behavior in model organisms such as mice and primates. While transgenic driver lines are powerful tools for studying CINs in mice, this technology is limited in other species. An alternative approach is to use viral vectors such as AAV, which can be used in multiple species including primates and also have potential for therapeutic use in humans. Thus, we sought to discover gene regulatory enhancer elements (REs) that can be used in viral vectors to drive expression in specific cell types. The present study describes the systematic genome-wide identification of putative REs (pREs) that are preferentially active in immature CINs by histone modification chromatin immunoprecipitation and sequencing (ChIP-seq). We evaluated two novel pRE...

Brain networks underlying states of social and sensory alertness are normally adaptive, influenced by serotonin and dopamine (DA), and abnormal in neuropsychiatric disorders, often with sex-specific manifestations. Underlying circuits, cells, and molecules are just beginning to be delineated. Implicated is a subtype of serotonergic neuron denoted Drd2-Pet1 , distinguished by expression of the type-2 DA receptor ( Drd2 ) gene, inhibited cell-autonomously by DRD2 agonism in slice, and, when constitutively silenced in male mice, affects levels of defensive and exploratory behaviors ([Niederkofler et al., 2016][1]). Unknown has been whether DRD2 signaling in these Pet1 neurons contributes to their capacity for shaping defensive behaviors. To address this, we generated mice in which Drd2 gene sequences were deleted selectively in Pet1 neurons. We found that Drd2Pet1-CKO males, but not females, demonstrated increased winning against sex-matched controls in a social dominance assay. Drd2Pet1-CKO females, but not ...

Children’s sensitivity to regularities within the linguistic stream, such as the likelihood that syllables co-occur, is foundational to speech segmentation and language acquisition. Yet, little is known about the neurocognitive mechanisms underlying speech segmentation in typical development and in neurodevelopmental disorders that impact language acquisition such as autism spectrum disorder (ASD). Here, we investigate the neural signals of statistical learning in 15 human participants (children ages 8–12) with a clinical diagnosis of ASD and 14 age-matched and gender-matched typically developing peers. We tracked the evoked neural responses to syllable sequences in a naturalistic statistical learning corpus using magnetoencephalography (MEG) in the left primary auditory cortex, posterior superior temporal gyrus (pSTG), and inferior frontal gyrus (IFG), across three repetitions of the passage. In typically developing children, we observed a neural index of learning in all three regions of interest (ROIs), ...

The autonomic nervous system (ANS) modulates the immune response through the engagement of an anti-inflammatory reflex. There is controversy regarding which efferent branch of the ANS, sympathetic or parasympathetic, downregulates the intensity of the inflammatory response. Furthermore, how information about the immune status of the body reaches the CNS to engage this reflex remains unclear. The present study demonstrates the existence of a liver-spinal axis that conveys early circulating inflammatory information to the CNS in response to lipopolysaccharide (LPS) and serves as the afferent arm of a sympathetic anti-inflammatory reflex. Furthermore, brainstem and spinal cord visceral sensory neurons show a time-of-day-dependent sensitivity to the incoming inflammatory information, in particular, prostaglandins (PG). Consequentially, the liver-spinal axis promotes the retention of tumor necrosis factor α (TNFα) in the liver and spleen during the resting period, resulting in low plasmatic TNFα levels. Consist...

Understanding the cellular mechanisms of kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation including forms of transcranial electrical stimulation, interferential stimulation, and high-rate spinal cord stimulation (SCS). Yet, the well-established low-pass filtering by neuronal membranes suggests minimal neuronal polarization in respond to charge-balanced kHz stimulation. The hippocampal brain slice model is among the most studied systems in neuroscience and exhaustively characterized in screening the effects of electrical stimulation. High-frequency electric fields of varied amplitudes (1–150 V/m), waveforms (sinusoidal, symmetrical pule, asymmetrical pulse) and frequencies (1 and10 kHz) were tested. Changes in single or paired-pulse field EPSPs (fEPSP) in CA1 were measured in response to radial-directed and tangential-directed electric fields, with brief (30 s) or long (30 min) application times. The effects of kHz stimulation on ongoing endogenous network activity were tested ...

Highlighted Research Paper: [[A HIF1a-Dependent Pro-Oxidant State Disrupts Synaptic Plasticity and Impairs Spatial Memory in Response to Intermittent Hypoxia. Alejandra Arias-Cavieres, Maggie A. Khuu, Chinwendu U. Nwakudu, Jasmine E. Barnard, Gokhan Dalgin and Alfredo J. Garcia III][2]][2] []: /lookup/doi/10.1523/ENEURO.0024-20.2020

Taste buds are maintained via continuous turnover of taste bud cells derived from local epithelial stem cells. A transcription factor Skn-1a (also known as Pou2f3) is required for the generation of sweet, umami (savory), and bitter taste cells that commonly express TRPM5 and CALHM ion channels. Here, we demonstrate that sodium–taste cells distributed only in the anterior oral epithelia and involved in evoking salty taste also require Skn-1a for their generation. We discovered taste cells in fungiform papillae and soft palate that show similar but not identical molecular feature with sweet, umami, and bitter taste-mediated Type II cells. This novel cell population expresses Plcb2 , Itpr3 , Calhm3 , Skn-1a , and ENaC α (also known as Scnn1a ) encoding the putative amiloride-sensitive (AS) salty taste receptor but lacks Trpm5 and Gnat3 . Skn-1a -deficient taste buds are predominantly composed of putative non-sensory Type I cells and sour-sensing Type III cells, whereas wild-type taste buds include Type II (i....

The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy and is currently seen as one of the few viable approaches to the treatment of a plethora of metabolic and neurodegenerative diseases. Empirical evidence notwithstanding, there is still no universal understanding of KD mechanism(s). An important fact is that the brain is capable of using ketone bodies for fuel. Another critical point is that glucose’s functions span beyond its role as an energy substrate, and in most of these functions, glucose is irreplaceable. By acting as a supplementary fuel, ketone bodies may free up glucose for its other crucial and exclusive function. We propose that this glucose-sparing effect of ketone bodies may underlie the effectiveness of KD in epilepsy and major neurodegenerative diseases, which are all characterized by brain glucose hypometabolism.