Inter-organelle contact sites have become increasingly appreciated as important regulators of cellular homeostasis, and disruption of inter-organelle contact site dynamics and function has been observed in various pathologies. Recently, inter-organelle contact sites between mitochondria and lysosomes were discovered, offering a new mechanism by which these two organelles may directly interact,...
Brain network organization, the emergence of cognition, and the accumulation of neurodegenerative pathology are interwoven concepts frequently studied under the umbrella of behavioral neurology, neuropsychiatry, neuropsychology, and neuropathology. One approach to studying the organization of cognitive processes is to study those with selective deficits in such networks. To understand how...
Research on how sleep contributes to memory has blossomed in recent years. These studies have generally focused on whether or not sleep impacts various types of memory independently. An open question is whether sleep interactively influences different memory types. My research focuses on two types of memory—specificity and generalization. Whereas...
Store-operated Ca2+ entry (SOCE) is a principal mechanism for generating cellular Ca2+ signals. Store-operated Ca2+ release-activated Ca2+ (CRAC) channels serve an essential role in generating Ca2+ elevations needed for transcriptional, enzymatic, and secretory effector cascades in many cell types. CRAC channels, comprised of the ER Ca2+ sensor STIM and the...
Movement is achieved by combining synaptic inputs from various sources and activating motor unit populations. Motor units are the quantal elements of motor control which act as a neuromechanical transducer that converts sensory inputs into motor output. Because of the tight neuromuscular junctions between motoneuron axon terminals and a large...
The hippocampus has been identified as a critical structure for supporting spatial memory processes in both humans and animals alike. Many of these processes such as the ability to self-localize in a given environment as well as engage in goal-directed navigation are thought to depend on the location-specific firing of...
Protein homeostasis, or proteostasis, is essential for preserving all cellular functions and involves a balance of protein synthesis, folding, trafficking, and degradation. A collapse in proteostasis is a common feature of many neurodegenerative disorders that are characterized by the accumulation of insoluble protein aggregates in the brain. Parkinson’s disease (PD)...
New neurons are continuously produced in the subgranular zone of the dentate gyrus of the hippocampus throughout life. These newborn dentate granule cells (DGCs) undergo a stereotyped process of morphological and functional maturation during the first few weeks after differentiation that recapitulates some aspects of postnatal neuronal development. The inhibitory...
Dynamic decision-making is a complex process that relies on our ability to generate, evaluate and implement a variety of strategies. Understanding how people navigate this process is a difficult problem that requires a wide range of methodologies. This study details a combination of behavioral experiments, computational modeling, and neuroimaging that...
The dentate gyrus is the first region for information processing within the classic hippocampal trisynaptic circuit, and this position makes it an important structure for the formation of associative memories. The dentate gyrus contains two major types of excitatory neurons: granule cells and mossy cells. While previous work has shown...
The basal ganglia are a remarkably complicated and interconnected tangle of subcortical nuclei whose exact function and composition are hotly debated to this day. What is plainly obvious, however, is that loss of dopaminergic modulation in the basal ganglia, as is the case in Parkinson’s disease (PD) following the progressive...
After stroke, inappropriate muscle activity phasing during the locomotor cycle is a key contributor to locomotor impairment. Muscle phasing has been shown to vary between behaviors post-stroke, but the degree to which individuals can voluntarily modulate activity is unclear. This dissertation consists of a series of three studies that investigate...
The mammalian retina contains three classes of photoreceptors: rods, cones and the recently discovered intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs express the photopigment melanopsin and were initially thought to be a homogeneous population of cells that drive subconscious visual behaviors such as circadian photoentrainment and pupil constriction. However, recent...
The cerebellum is involved in sensorimotor processing and motor control in the brain. What has been found across many species for many behaviors is cerebellar Purkinje (Pkj) cells and cerebellar nuclear (CbN) cells show activity that is related to and predictive of movements. Less is known about how patterns of...
Identifying key molecular mechanisms and targets for therapeutic development in sporadic neurodegenerative diseases has been challenging. Therefore, in-depth investigation of genetic forms of disease can provide valuable insight into pathogenic disease mechanisms. The discovery of genetic forms of Parkinson’s disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative...
Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are two devastating neurodegenerative diseases that affect 100,000s of people globally. They have a severe adverse impact on society, yet there are currently no early diagnostic tools or disease-modifying therapies available. Despite their clinical heterogeneity, evidence points to these diseases being on...
The exchange of information in the brain is accomplished through sequences of action potentials that result from the integration of local microcircuits. Unraveling the connectivity of the neurons that constitute these microcircuits and how they contribute to network activity is vital for understanding how information is relayed through the brain...
Voltage-gated Na channels are expressed in all neurons, and are responsible for the upstroke of the action potential. They are part of a complex of proteins that includes pore-forming α subunits and auxiliary subunits that modify their trafficking, gating, and function. The modulation of Na channels by auxiliary subunits is...
We have a remarkable ability to perform complex, coordinated movements without much conscious effort. In addition to the computations required to generate commands for muscles, a key aspect of coordinated motor control is incorporating sensory feedback about the movement. One of the most important feedback routes is through proprioception, the...
Leptin, a peptide mainly secreted in proportion to adipose tissue mass, increases energy expenditure with a parallel increase in breathing. The existence of a leptin-mediated neural circuit linking breathing to metabolism has been speculated, yet the precise central mechanisms were unknown. In my thesis, I show that optogenetic activation of...
The interaction of amyloid-β (Aβ) with endogenous metal ions is thought to play a role in the pathogenesis of Alzheimer’s disease (AD). However, limited tools exist to study and modulate Aβ-metal binding. The Meade lab has developed cobalt(III) Schiff base (Co(III)-sb) complexes as protein inhibitors that competitively displace metals from...
Birds such as the barn owl and zebra finch are known for their remarkable hearing abilities that are critical for survival, communication and vocal learning functions. A key to achieving these hearing abilities is the speed and precision required for the temporal coding of sound; a process heavily dependent on...
The brain is known to shrink in normal aging or neurodegenerative disease and yet the neurobiological underpinnings of the cortical atrophy remain elusive. The structural changes that represent cortical atrophy can be measured during life using the reliable and quantitative method known as magnetic resonance imaging (MRI). Primary progressive aphasia...
Frontotemporal dementia (FTD) encompasses a group of neurodegenerative disorders characterized by cognitive and behavioral impairments. Heterozygous mutations in progranulin (PGRN) cause familial FTD and result in decreased PGRN expression, while homozygous mutations result in complete loss of PGRN expression and lead to the neurodegenerative lysosomal storage disorder neuronal ceroid lipofuscinosis...
Understanding associative memory is fundamental for a variety of neurological and neurodegenerative diseases, however, a large proportion of this research has excluded female subjects due to unsubstantiated bias. By including intact females, ovariectomized females and males in the study of associative memory, clear sex differences in acquisition emerged. Female mice...
For years, neuroscientists have strived to understand memory consolidation, where salient memories are sorted and organized into distributed cortical networks for long-term storage. A large body of sleep research suggests that slow-wave sleep is an optimal opportunity for memory consolidation, and that consolidation is driven, at least in part, by...
Coordinated movement relies on the precise and controlled activation of populations of motor units, which convert the commands of the nervous system into muscle forces. Motor unit firing patterns are often nonlinear and generated through the response to a combination of ionotropic excitatory and inhibitory commands, as well as metabotropic...
Navigating through the world is typically a multisensory experience. Mammals are believed to navigate using a cognitive map of space stored in the hippocampus. Yet, it is unclear how and whether spatial information of different sensory modalities can contribute to this map. A major barrier to addressing this question has...
Interactions between working memory and long term memory systems are still not well understood, as the systems have long been thought to be mostly separate. An interesting intersection of these memory systems is domain-specific expertise, whereby individuals are able to show supra-span memory for information related to the area of...
Understanding associative memory is fundamental for a variety of neurological and neurodegenerative diseases, however, a large proportion of this research has excluded female subjects due to unsubstantiated bias. By including intact females, ovariectomized females and males in the study of associative memory, clear sex differences in acquisition emerged. Female mice...
Rhythmic fluctuations of electrical activity in the brain provide insights into the proposed mechanism by which we encode experiences and then maintain, forget, modify, and retrieve them. Yet there is still much to learn about how neural oscillations relate to memory function. The purpose of this research is to discover...
Basal ganglia are a highly interconnected group of nuclei involved in motor control. The external globus pallidus (GPe) is a critical node within the basal ganglia circuit. While the prevailing basal ganglia circuit model assumes the GPe as merely a relay, phasic changes in the activity of GPe neurons during...
Individuals following a stroke suffer from a host of movement impairments that affect the upper extremity. Hand use is often significantly compromised, especially in individuals with more severe impairments, which makes it difficult for individuals to participate in activities of daily living. One of the major goals of rehabilitation is...
Classical conditioning is a form of associative learning and can be used as a behavioral paradigm to model and investigate the neural mechanisms underlying associative learning. In this work, classical conditioning paradigms are used to test the effectiveness of a disease model on the impact of learning and emotional regulation...
Movement and sensing fundamentally works in a synergistic manner. Animal's sensory organs --- be they independently movable like eyes or requiring whole body movement as in the case of electroreceptors --- are actively manipulated throughout stimulus-driven active sensing behaviors. Though these sensing-related motions have been individually reported and analyzed across...
Prions are self-perpetuating, alternative protein conformations associated with neurological diseases and normal cellular functions. Saccharomyces cerevisiae contains many endogenous prions – providing a powerful system to study prionization. Previously, the Li Lab demonstrated that Swi1, a component of the SWI/SNF chromatin-remodeling complex, can form the prion [SWI+]. A small region,...
The presence of subjective cognitive decline (SCD) among cognitively normal-for-age older adults is increasingly hypothesized to represent a preclinical stage in the development of Alzheimer’s dementia (Jessen et al., 2014). This project aimed to characterize this construct with regard to its cognitive, motor, emotional, and functional features. The first study...
Stroke is the leading cause of permanent adult disability. Subcortical unilateral (hemiparetic) stroke affecting the internal capsule or basal ganglia is the most common of all strokes and usually results in hemiparesis of the contralateral arm and leg. About 80% of the individuals with a moderate to severe hemiparetic stroke...
Contactin associated protein like 2 (CNTNAP2) has emerged as a prominent susceptibility gene implicated in multiple complex neurodevelopmental disorders, including autism spectrum disorders (ASD), intellectual disability (ID), and schizophrenia (SCZ). The presence of seizure comorbidity in many of these cases, as well as inhibitory neuron dysfunction in Cntnap2 knockout (KO)...
Mitochondria-lysosome contacts are recently identified sites for mediating crosstalk between both organelles, but their role in normal and diseased human neurons remains unknown. We used super-resolution and live-cell microscopy in human iPSC-derived neurons to demonstrate that mitochondria-lysosome contacts can dynamically form in the soma, axons, and dendrites of human neurons,...
Background: Glioblastoma (GBM) tumors are the most malignant brain cancers and are characterized as Grade IV astrocytomas by the World Health Organization. GBM tumors can be classified into three molecular subtypes known as proneural, classical, and mesenchymal. In addition, GBM tumors also have a small population of cells known as...
Episodic memory provides a means by which we are able to reflect on the past, make decisions about the future, and form a learned identity. Even subtle changes to our memory can have a detrimental impact on our daily lives. Memory declines as we age, and clinically salient impairment is...
In the vertebrate retina, neurons process visual signals, generating feature selectivity in their activity levels. We use computational models to understand these behaviors by interpreting them mathematically. One component of this analysis is the spatial selectivity or receptive field, a property found in all visual sensory neurons. The neurons found...
Episodic memory provides a means by which we reflect on the past, make decisions about the future, and form a learned identity. Episodic memory depends on the hippocampus as well as on the distributed set of regions that form a hippocampal-cortical network (HCN), including medial prefrontal, posterior cingulate, and medial...
Motor planning is fundamental to the performance of everyday reaching movements. The influence of planning is not limited to voluntary movements but extends to involuntary movements initiated in response to sensory stimuli, such as postural perturbations applied to the arm. Stroke alters voluntary reaching and the involuntary response to perturbations,...
Compromised protein homeostasis underlies accumulation of plaques and tangles in Alzheimer’s disease (AD); however, little is known about the early mechanisms that contribute to this process. To objectively assess protein turnover at early stages of amyloid beta (Aβ) proteotoxicity, we used dynamic metabolic labeling with stable isotopes followed by proteomic...
One of the most fascinating observations in the brain is that the neural connections change with experience and this phenomenon is called synaptic plasticity. Patterns of activity or neuromodulators can acutely induce changes in the synaptic strength in the brain. My thesis is focused on understanding the mechanisms of plasticity...
Maneuvering your limbs requires both accurate commands for how to move, and accurate feedback of their true movements. Conventional prosthetic arms currently lack this sense of proprioceptive feedback, which can make daily tasks difficult without close visual monitoring. Although studies have successfully provided artificial proprioceptive feedback to improve control, this...
To survive, animals, including human beings, have developed an amazing ability to learn the constantly changing environment. Specifically, detecting specific odorants in a noisy, variable background is crucial for finding food and water, mating, and avoiding potential dangers. For this purpose, rodents have developed an olfactory system that is powerful...
In susceptible individuals, episodic memories of overwhelmingly stressful experiences can give rise to debilitating socio-affective symptoms, including social dysfunction. This occurs even when such memories are not easily accessed for retrieval. In this case, it is generally accepted that the restricted retrieval of such memories is due to their having...
We present two ways in which measures of information can be used for the design and analysis of neural networks in both the brain and the computer. In the brain, stimulus is often represented as a distributed pattern of activity in a network of neurons. The quality of such population...
This thesis focuses on the development of a cochlear implant (CI) that uses photons to stimulate surviving auditory neurons in severe-to-profoundly deaf individuals. The benefit of optical over electrical stimulation is its spatial selectivity with the potential to create significantly more independent channels to encode acoustic information and likely enhances...
We perform many movements every day without much deliberation. However, moving can be seen as a form of decision-making since one of many possible movements must be selected and executed. The decision-making processes that underlie movements are influenced by various factors, including sensory perception, energetics, time, perceived rates of failure...
Neurons are sensitive to the mechanical properties of their environment and show better growth, survival and differentiation when they are cultured in soft environments with mechanical properties similar to those of the brain compared to other tissues. Within the central nervous system (CNS), there is also a range of mechanical...
Neurodegenerative diseases (NDs) commonly involve the accumulation and aggregation of neurotoxic proteins that impair and ultimately destroy specific neurons. Considerable evidence from human and animal studies indicates that many NDs show disrupted circadian and sleep as symptoms. Yet little is known about the molecular mechanisms by which genes cause NDs...
Recent studies have begun to examine white matter connectivity aberrations in psychiatric populations, such as major depressive disorder. Several studies have found reduced white matter integrity (WMI) in depressed samples, though the location of this reduction is not clear. Incorporating symptom measures of depression severity and rumination may allow for...
Many species of rodents rely on the set of exquisitely sensitive facial vibrissae (whiskers) to guide rich behaviors in which other senses are inadequate. Although whiskers are, like all hairs, inert strands of keratin, they provide the animal with a rich landscape of tactile information which is used to guide...
The retina does not act as a simple camera, rather visual information goes through multiple layers of processing before it reaches the brain. Retinal ganglion cells (RGCs) are the output neurons of the retina and process visual information in the retina and then project into the brain. There are over...
Slow-wave sleep (SWS) is important for overall health since it affects many physiological pathways from cardio-metabolic health to cognitive function. Sleep and autonomic nervous system (ANS) functioning are closely coupled at anatomical and physiological levels. Sleep-related changes in ANS function are likely the main pathway through which SWS affects many...
The apolipoprotein E (APOE) E4 isoform is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). While APOE is predominantly expressed by astrocytes in the central nervous system, neuronal expression of APOE is of increasing interest in age-related cognitive impairment, neurological injury, and neurodegeneration. Here we show that endogenous...
Rhythmic oscillations in the brain are widespread. Extracellular recordings of local field potentials (LFPs) using methods ranging from microelectrodes to scalp electroencephalography (EEG) have demonstrated that oscillatory dynamics play a vital role in operations such as network synchronization, sensory tuning and information packaging. Empirical and computational evidence suggest that these...
Decision making is an essential and indispensable element in everyday life. It is posited that parallel, distinct systems subserving deliberative, goal-directed control and automatic, habitual control underlie decision making. Computational accounts suggest that model-based and model-free learning strategies give rise to these two systems respectively. The model-based system is a...
Spinal cord injury (SCI) is a devastating injury, which can be caused by motor vehicle accidents, violence, and non-traumatic causes. These injuries can leave patients with lifelong paralysis, as well as incontinence and life threatening autonomic dysreflexia. There is currently no FDA approved treatment for SCI. Spinal injury disrupts the...
Anxiety and depression are highly prevalent, recurrent, and major public health problems. Decades of research has uncovered associations between symptom dimensions of anxiety and depression and abnormal neural activation across executive control-, threat-, and reward-related networks. Recent studies have developed a hierarchical symptom structure of anxiety and depression termed the...
We present a biophysical model of GCaMP6f calcium fluorescence in CA1 pyramidal neuron dendrites based upon results from imaging and electrophysiology experiments. This work was completed using experimental results from the laboratory of Professor Daniel Dombeck, Department of Neurobiology. Constraining the model to reproduce different objectives --- from in-vitro and...
Numerous insights into the sensorimotor systems that guide the control of voice have been garnered by observing how the system responds to manipulations of its auditory feedback. However, current approaches may be limited in the exploration of more complex parameters of volitional and adaptive voice control due to their limited...
The cerebellar cortical system is an extensively studied circuit which is critical for motor learning. While multiple monoamines, such as norepinephrine and serotonin, modulate cerebellar cortical output, the mechanistic details of dopaminergic signaling in the cerebellum remain poorly understood. Additionally, neuronal cell types residing within the cerebellum remain relatively under-characterized....
Background: The way in which one perceives their visual world (i.e., bottom-up visual perception) and what one pays attention to in their surroundings (i.e., top-down attention), are critical to uncovering underlying thoughts and cognitions, and impact how one operates in the social world. Individuals with autism spectrum disorder (ASD), a...
My research at northwestern with Dr. Christina Zelano focused on the human amygdala subnucleithat receive monosynaptic input from the olfactory bulb. Surprisingly little is known
about these brain regions, including their potential roles in olfactory and nonolfactory
processing. During my PhD, I completed three projects aimed at furthering our understanding...
Herpes simplex virus (HSV) encephalitis (HSE) is the most common cause of sporadic fatal encephalitis, and despite targeted antiviral therapy, outcomes remain poor. While rare in adults, neonates are significantly more susceptible to severe HSV disease. Understanding both the host and viral factors that contribute to pathogenesis is critical to...
In the adult hippocampus of many mammalian species, populations of newborn dentate granule cells (DGCs) are continuously generated and undergo subsequent activity-dependent neuronal maturation and incorporation into the preexisting hippocampal circuitry. Increasing evidence has demonstrated that these young adult-born DGCs (abDGCs) participate in numerous cognitive and affective processes such as...
All animals purposefully navigate feature-rich environments: while exploring, in search of vital resources of food and water, finding mates, and patrolling and marking habitats. During these complex behaviors, continuous analogue input information from peripheral sensory organs guides discrete and digital sequential motor output; accordingly, each action is informed, modulated, or...
Sensorimotor integration is a general term to describe how task-specific motor output is generated from the selective and rapid processing of sensory and motor information. The rodent vibrissal (whisker) system is an important model for the study of sensorimotor integration and active tactile sensing. This research uses the rodent vibrissal...
In mature neurons, postsynaptic NMDARs are segregated into two populations, synaptic and extrasynaptic NMDARs, which differ in localization, function, and associated intracellular cascades. These two pools are connected via lateral diffusion, and receptor exchange between them modulates synaptic NMDAR content (NMDAR-plasticity). Here, we identify the phosphorylation of the PDZ-ligand of...
In memory overgeneralization, details from negatively-valenced episodic memories become excessively generalized to unrelated neutral situations. This is a key cognitive distortion associated with major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Stress promotes memory generalization, and this process likely relies on stress-induced changes in dorsal...
Chemokines, such as Stromal Derived Factor 1 (SDF-1 or CXCL12) and their G protein coupled receptors (GPCRs) are well known regulators of the development and functions of numerous tissues. CXCL12 has two receptors: CXCR4 and CXCR7 or atypical chemokine receptor 3 (ACKR3). CXCR7 has been described as an atypical “biased”...
Social engagement, or shared attention between a child and caregiver, is a critical process for language and social development. Although previous EEG studies have investigated child social processing in closely controlled, experimental studies, no study has examined the interactive, reciprocal process of naturalistic social engagement. In my first paper, we...
Dystonia is a movement disorder characterized by involuntary and repetitive co-contractions of the agonist and antagonist muscles. Dystonia 6 (DYT6) is an autosomal dominant dystonia caused by loss of function mutations in the zinc finger transcription factor THAP1. I have generated Thap1 knock-out mice with a view to understanding its...
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are non-selective cation channels expressed in the brain and heart where they exert control over many diverse physiological properties. In the hippocampus, HCN channels are enriched in a dendritic gradient within CA1 pyramidal cells where they reduce dendritic integration and dampen neuronal excitability. HCN channels...
Decisions in naturalistic environments usually feature delayed and uncertain outcomes that can only be reached after a sequence of actions are performed. For example, canonical stalking and pursuit strategies used by terrestrial predators often involve stages of concealment, pauses where the predator remains motionless, and high speed chase sequences. The...
Considerable progress has been made in characterizing the neural circuits that underlie stress, fear, feeding, and pain. However, little is known about how they affect each other. Stress bidirectionally regulates feeding, either increases (e.g., stress-induced binge eating) or decreases (e.g., stress-induced anorexia), depending on the types of stressors, duration of...
Stimulus generalization is a critical mechanism for facilitating behavioral flexibility. Generalization allows the brain to reduce computational demands that would otherwise be necessary to create unique representations for each and every encounter while allowing the ability to deal with the complexity of real-world situations. Stimulus generalization is a fundamental cognitive...
A one-time, unilateral injury to the developing brain can interrupt the typical process of development and result in motor impairments that evolve over the course of the whole life-span. The timing of injury relative to neural development has implications for the continued refinement of the nervous system and the descending...
Coiled-coil helix coiled-coil helix domain containing 10 (CHCHD10) is a nuclear gene that encodes for a mitochondria-enriched protein of unknown function. This type of protein is typically imported into mitochondria via the disulfide relay system which facilitates the formation of disulfide bridges between each coiled-coil helix, resulting in maintenance of...
The hippocampus has a well-established role in episodic memory and serves as a hub in a network of distributed brain regions (i.e., hippocampal-cortical network; HCN). Theta-band (4-8 Hz) neural activity recorded in the hippocampus have been associated with memory processing, and synchronized theta oscillations among the hippocampus and HCN regions...
Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) represent a class of non-canonical, ganglion cell photoreceptors. These cells influence a variety of visual behaviors including contrast sensitivity, circadian photoentrainment, sleep, and even mood. These wide-ranging behavioral influences are attributed to the multiple subtypes (M1-6) that comprise the ipRGC population, with different...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron (MN) degeneration and resulting in progressive paralysis and death. ALS is genetically heterogeneous, disease pathophysiology is not completely understood, and there are no effective drug therapies. To develop broadly applicable therapeutics, we examine disease mechanisms in the...
Cholinergic modulation of the brain cortex is critical for cognitive processes, and altered cholinergic modulation of the prefrontal cortex is emerging as an important mechanism of neuropathic pain. Despite the known sex differences in pain prevalence and perception, the precise nature of the mechanisms responsible for sexual dimorphism in chronic...
The answer to the question “Why do we sleep?” lies in understanding the biological underpinnings of homeostatic drive to sleep. Wakefulness is correlated with numerous changes in brain activity, structure and gene/protein expression that re-normalize following sleep however which of these elements is sufficient to cause sleep drive and how...
Perturbations to the physiology or impairments in the formation of synapses within the cochlea, specifically the ribbon synapses, result in decreased sensitivity to auditory stimuli. In example, prolonged exposure to moderately intense auditory stimuli, like power tools, can result in the swelling of nerve terminals, retraction of the postsynaptic membrane,...
Affect represents a major domain of human consciousness, consisting of a complex group of psychophysiological processes to drive human behavior. Many genetic and environmental factors may cause dysregulation of affective states, resulting in disorders that severely disrupt normal cognitive function and diminish the quality of life. Transitions among affective states...
The current view in neuroscience holds that the brain, together with its sensory and motor structures and the environment, form a closed-loop system – a sensorimotor loop – in which the brain receives information from the environment and converts it into a motor response while simultaneously making predictions about future...
Research over the past several decades has revealed that memory reactivation in sleep contributes to the formation of long-lasting memories. Among the most recent developments in this field is the widespread use of the technique of targeted memory reactivation (TMR), which allows researchers to induce reactivation of specific memories during...
Human olfactory function is important for a myriad of behaviors, including food seeking, social cognition, memory, emotional regulation, and detecting environmental threats. In animal models, particularly dense olfactory inputs have been shown to target orbitofrontal cortex (OFC), a region involved in multimodal sensory integration, reward coding, and flexibly guiding our...
Aging is the greatest known risk factor for Alzheimer’s Disease (AD); however, the molecular mechanisms underlying aging and how it can initiate and or exacerbate AD, is still unknown. Epigenetic regulation has been widely accepted to play an essential role in aging or AD-related processes; however, whether dysregulations of histone...
Voltage-gated potassium (KV) currents play a crucial role in shaping and controlling the firing patterns that serve as the fundamental basis for the differential signal processing from the ear to the auditory cortex, with distinct firing patterns observed with high- and low-frequency phenotypes. This is an interesting phenomenon, in the...
Electrical spinal cord stimulation is an emerging treatment for spinal cord injury that can improve walking and bladder control, among many other functions. While the anatomical location of the motor pools for muscles involved in locomotion in the lumbosacral cord has been identified, the map of the functional output of...
Persons with spinal cord injuries can use state-of-the-art brain-computer interfaces to control robotic arms. Despite this high-tech solution, their movements are slow and imprecise, much like those made by individuals who have lost proprioception, the sense of body position and movement. Intracortical microstimulation (ICMS) used to reactivate neural circuits in...
Over the course of disease progression, half of adults with type II diabetes also develop diabetic peripheral neuropathy (DPN), peripheral nerve damage precipitated by the downstream metabolic effects of hyperglycemia, insulin resistance, and dyslipidemia. This multifactorial pathogenesis of DPN leads to various structural and physiological changes within the nerve, ultimately...
Voltage-gated potassium (KV) currents play a crucial role in shaping and controlling the firing patterns that serve as the fundamental basis for the differential signal processing from the ear to the auditory cortex, with distinct firing patterns observed with high- and low-frequency phenotypes. This is an interesting phenomenon, in the...
