Rhythms are a common feature of brain activity. Across different types of rhythms, the phase has been proposed to have functional consequences, thus requiring its accurate specification from noisy data. Phase is conventionally specified using techniques that presume a frequency band-limited rhythm. However, in practice, observed brain rhythms are typically nonsinusoidal and amplitude modulated. How these features impact methods to estimate phase remains unclear. To address this, we consider three phase estimation methods, each with different underlying assumptions about the rhythm. We apply these methods to rhythms simulated with different generative mechanisms and demonstrate inconsistency in phase estimates across the different methods. We propose two improvements to the practice of phase estimation: (1) estimating confidence in the phase estimate, and (2) examining the consistency of phase estimates between two (or more) methods.

Sympathetic preganglionic neurons (SPNs) are the final output neurons from the central arm of the autonomic nervous system. Therefore, SPNs represent a crucial component of the sympathetic nervous system for integrating several inputs before driving the postganglionic neurons (PGNs) in the periphery to control end organ function. The mechanisms which establish and regulate baseline sympathetic tone and overall excitability of SPNs and PGNs are poorly understood. The SPNs are also known as the autonomic motoneurons (MNs) as they arise from the same progenitor line as somatic MNs that innervate skeletal muscles. Previously our group has identified a rich repertoire of homeostatic plasticity (HP) mechanisms in somatic MNs of the embryonic chick following in vivo synaptic blockade. Here, using the same model system, we examined whether SPNs exhibit similar homeostatic capabilities to that of somatic MNs. Indeed, we found that after 2-d reduction of excitatory synaptic input, SPNs showed a significant increase ...

Brains implement some of the most complex functions of living systems including intelligence, decision-making, learning, and sentience, which is the capacity for subjective experience. To better understand these and other cognitive functions, neuroscientists have meticulously delineated the brain’s microcircuitry and pathways to relate mental phenomena with discrete neural substrates. One of the driving forces behind what has become an ever-expanding literature on functional neuroanatomy is the longstanding assumption that all mental actions and states can be localized, mapped, or otherwise attributed to specific configurations of brain matter. Consistent with this assumption, by selectively damaging or stimulating brain regions, one could suppress or evoke cognitive or behavioral responses that confirmed suspected structure-function relationships. While this approach has not helped explain why mind emerges from matter, its historical success is a crowning achievement for the field of cognitive neuroscienc...

Chronic stress has been considered to induce depressive symptoms, such as anhedonia, particularly in susceptible individuals. Synaptic plasticity in the prefrontal cortex (PFC) is closely associated with susceptibility or resilience to chronic stress-induced anhedonia. However, effects of chronic stress with different durations on the neurobiological mechanisms that underlie susceptibility to anhedonia remain unclear. The present study investigated effects of chronic mild stress (CMS) for 14, 21, and 35 d on anhedonia-like behavior and glutamate synapses in the PFC. We found that brain-derived neurotrophic factor (BDNF) levels in the PFC significantly decreased only in anhedonia-susceptible rats that were exposed to CMS for 14, 21, and 35 d. Additionally, 14 d of CMS increased prefrontal glutamate release, and 35 d of CMS decreased glutamate release, in addition to reducing synaptic proteins and spine density in the PFC. Moreover, we found that anhedonia-like behavior in a subset of rats spontaneously decr...

Mitochondria are integrative hubs central to cellular adaptive pathways. Such pathways are critical in highly differentiated postmitotic neurons, the plasticity of which sustains brain function. Consequently, defects in mitochondria and in their dynamics appear instrumental in neurodegenerative diseases and may also participate in cognitive impairments. To directly test this hypothesis, we analyzed cognitive performances in a mouse mitochondria-based disease model, because of haploinsufficiency in the mitochondrial optic atrophy type 1 (OPA1) protein involved in mitochondrial dynamics. In males, we evaluated adult hippocampal neurogenesis parameters using immunohistochemistry. We performed a battery of tests to assess basal behavioral characteristics and cognitive performances, and tested putative treatments. While in dominant optic atrophy (DOA) mouse models, the known main symptoms are late onset visual deficits, we discovered early impairments in hippocampus-dependent spatial memory attributable to defe...

Animals exhibit context-dependent behavioral decisions that are mediated by specific motor circuits. In social species these decisions are often influenced by social status. Although social status-dependent neural plasticity of motor circuits has been investigated in vertebrates, little is known of how cellular plasticity translates into differences in motor activity. Here, we used zebrafish ( Danio rerio ) as a model organism to examine how social dominance influences the activation of swimming and the Mauthner-mediated startle escape behaviors. We show that the status-dependent shift in behavior patterns whereby dominants increase swimming and reduce sensitivity of startle escape while subordinates reduce their swimming and increase startle sensitivity is regulated by the synergistic interactions of dopaminergic, glycinergic, and GABAergic inputs to shift the balance of activation of the underlying motor circuits. This shift is driven by socially induced differences in expression of dopaminergic receptor...

Because of the legalization of Cannabis in many jurisdictions and the trend of increasing Δ9-tetrahydrocannabinol (THC) content in Cannabis products, an urgent need exists to understand the impact of Cannabis use during pregnancy on fetal neurodevelopment and behavior. To this end, we exposed female Sprague Dawley rats to Cannabis smoke daily from gestational day 6 to 20 or room air. Maternal reproductive parameters, offspring behavior, and gene expression in the offspring amygdala were assessed. Body temperature was decreased in dams following smoke exposure and more fecal boli were observed in the chambers before and after smoke exposure in dams exposed to smoke. Maternal weight gain, food intake, gestational length, litter number, and litter weight were not altered by exposure to Cannabis smoke. A significant increase in the male-to-female ratio was noted in the Cannabis -exposed litters. In adulthood, male and female Cannabis smoke-exposed offspring explored the inner zone of an open field significantl...

Stress has been identified as a major contributor to human disease and is postulated to play a substantial role in epileptogenesis. In a significant proportion of individuals with epilepsy, sensitivity to stressful events contributes to dynamic symptomatic burden, notably seizure occurrence and frequency, and presence and severity of psychiatric comorbidities [anxiety, depression, posttraumatic stress disorder (PTSD)]. Here, we review this complex relationship between stress and epilepsy using clinical data and highlight key neurobiological mechanisms including the hypothalamic-pituitary-adrenal (HPA) axis dysfunction, altered neuroplasticity within limbic system structures, and alterations in neurochemical pathways such as brain-derived neurotrophic factor (BNDF) linking epilepsy and stress. We discuss current clinical management approaches of stress that help optimize seizure control and prevention, as well as psychiatric comorbidities associated with epilepsy. We propose that various shared mechanisms o...

Most human navigation studies in MRI rely on virtual navigation. However, the necessary supine position in MRI makes it fundamentally different from daily ecological navigation. Nonetheless, until now, no study has assessed whether differences in physical body orientation (BO) affect participants’ experienced BO during virtual navigation. Here, combining an immersive virtual reality navigation task with subjective BO measures and implicit behavioral measures, we demonstrate that physical BO (either standing or supine) modulates experienced BO. Also, we show that standing upright BO is preferred during spatial navigation: participants were more likely to experience a standing BO and were better at spatial navigation when standing upright. Importantly, we report that showing a supine virtual agent reduces the conflict between the preferred BO and physical supine BO. Our study provides critical, but missing, information regarding experienced BO during virtual navigation, which should be considered cautiously ...

Every so often, I conclude that life is not possible. It is not uncommon for me to walk out of a seminar about the pathways and dynamics of biochemical signaling or the structure of biological molecules to conclude that the complexities of life processes defy imagination. Our ability to maintain a sense of wonder about the mysteries of biological mechanisms is what drives us as scientists, as otherwise wresting new insights from the recalcitrant world of interacting pathways would be too frustrating. So all successful biologists must, paradoxically, see both the proverbial forest and their trees, and recognize both the elegant simplicity and the confounds characteristic of living organisms. That sense of mystery and wonder is somewhat at odds with our common sense. It is common sense that is now too often lost, as we grapple with new technologies and large datasets in our science. As scientists, today, we must balance our common sense with our growing reliance on big data to extract the new insights about...