Medicine and Health Sciences Commons^™

Are There Place Cells In The Avian Hippocampus?, David F Sherry, Stephanie L Grella, Mélanie F Guigueno, David J White, Diano F Marrone

Brain and Mind Institute Researchers' Publications

Birds possess a hippocampus that serves many of the same spatial and mnemonic functions as the mammalian hippocampus but achieves these outcomes with a dramatically different neuroanatomical organization. The properties of spatially responsive neurons in birds and mammals are also different. Much of the contemporary interest in the role of the mammalian hippocampus in spatial representation dates to the discovery of place cells in the rat hippocampus. Since that time, cells that respond to head direction and cells that encode a grid-like representation of space have been described in the rat brain. Research with homing pigeons has discovered hippocampal cells, …

Positive Allosteric Modulator Of Gabab Receptor Alters Behavioral Effects But Not Afterdischarge Progression Induced By Partial Hippocampal Kindling., L Stan Leung, Miao Jin, Liangwei Chu, Jingyi Ma

Physiology and Pharmacology Publications

Hippocampal seizures decreased the function of GABAB receptors, which may further increase seizure susceptibility and contribute to development of schizophrenia-like behaviors. Recent literature indicates that GABAB receptor agonist may normalize schizophrenia-like behaviors and prevent drug-induced behavioral sensitization. We hypothesized that positive modulation of GABAB receptor function during seizure induction will reduce seizure-induced schizophrenia-like behaviors. Using a partial hippocampal kindling model, afterdischarges were induced after injection of saline or dimethyl sulfoxide (vehicle-kindled rats), or a GABAB receptor positive allosteric modulator CGP7930, at 1 mg/kg i.p. (CGP1-kindled) or 5 mg/kg i.p. (CGP5-kindled). The increase in the primary afterdischarge duration during kindling was …

Quantifying And Comparing The Pattern Of Thalamic And Cortical Projections To The Posterior Auditory Field In Hearing And Deaf Cats., Blake E Butler, Nicole Chabot, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following sensory loss, compensatory crossmodal reorganization occurs such that the remaining modalities are functionally enhanced. For example, behavioral evidence suggests that peripheral visual localization is better in deaf than in normal hearing animals, and that this enhancement is mediated by recruitment of the posterior auditory field (PAF), an area that is typically involved in localization of sounds in normal hearing animals. To characterize the anatomical changes that underlie this phenomenon, we identified the thalamic and cortical projections to the PAF in hearing cats and those with early- and late-onset deafness. The retrograde tracer biotinylated dextran amine was deposited in the …

Design, Development And Evaluation Of A Compact Telerobotic Catheter Navigation System., Mohammad Ali Tavallaei, Daniel Gelman, Michael Konstantine Lavdas, Allan C Skanes, Douglas L Jones, Jeffrey S Bax, Maria Drangova

Medical Biophysics Publications

BACKGROUND: Remote catheter navigation systems protect interventionalists from scattered ionizing radiation. However, these systems typically require specialized catheters and extensive operator training.

METHODS: A new compact and sterilizable telerobotic system is described, which allows remote navigation of conventional tip-steerable catheters, with three degrees of freedom, using an interface that takes advantage of the interventionalist's existing dexterity skills. The performance of the system is evaluated ex vivo and in vivo for remote catheter navigation and ablation delivery.

RESULTS: The system has absolute errors of 0.1 ± 0.1 mm and 7 ± 6° over 100 mm of axial motion and 360° of …

A Quantitative Comparison Of The Hemispheric, Areal, And Laminar Origins Of Sensory And Motor Cortical Projections To The Superior Colliculus Of The Cat., Blake E Butler, Nicole Chabot, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a …

Associative Spike Timing-Dependent Potentiation Of The Basal Dendritic Excitatory Synapses In The Hippocampus In Vivo., Thomas K Fung, Clayton S Law, L Stan Leung

Physiology and Pharmacology Publications

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing-generating synaptic excitation before a spike-results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of -10 …

Transient Pupil Dilation After Subsaccadic Microstimulation Of Primate Frontal Eye Fields., Sebastian J Lehmann, Brian D Corneil

Brain and Mind Institute Researchers' Publications

UNLABELLED: Pupillometry provides a simple and noninvasive index for a variety of cognitive processes, including perception, attention, task consolidation, learning, and memory. The neural substrates by which such cognitive processes influence pupil diameter remain somewhat unclear, although cortical inputs to the locus coeruleus mediating arousal are likely involved. Changes in pupil diameter also accompany covert orienting; hence the oculomotor system may provide an alternative substrate for cognitive influences on pupil diameter. Here, we show that low-level electrical microstimulation of the primate frontal eye fields (FEFs), a cortical component of the oculomotor system strongly connected to the intermediate layers of the …

Pulmonary Ct And Mri Phenotypes That Help Explain Chronic Pulmonary Obstruction Disease Pathophysiology And Outcomes, Eric A Hoffman, David A Lynch, R Graham Barr, Edwin J R Van Beek, Grace Parraga

Medical Biophysics Publications

Pulmonary x-ray computed tomographic (CT) and magnetic resonance imaging (MRI) research and development has been motivated, in part, by the quest to subphenotype common chronic lung diseases such as chronic obstructive pulmonary disease (COPD). For thoracic CT and MRI, the main COPD research tools, disease biomarkers are being validated that go beyond anatomy and structure to include pulmonary functional measurements such as regional ventilation, perfusion, and inflammation. In addition, there has also been a drive to improve spatial and contrast resolution while at the same time reducing or eliminating radiation exposure. Therefore, this review focuses on our evolving understanding of …

Differential Effect Of Clomipramine On Habituation And Prepulse Inhibition In Dominant Versus Subordinate Rats., Alvin Yang, Tahira Daya, Karen Carlton, Jin Hui Yan, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Many patients with depression have comorbidities associated with an impairment of sensorimotor gating, such as e.g. schizophrenia, Parkinson Disease, or Alzheimer disease. Anti-depressants like clomipramine that modulate serotonergic or norepinephrinergic neurotransmission have been shown to impact sensorimotor gating, it is therefore important to study potential effects of clomipramine in order to rule out an exacerbation of sensorimotor gating impairment. Prior studies in animals and humans have been inconclusive. Since serotonin and norepinephrine levels are closely related to anxiety and stress levels and therefore to the social status of an animal, we tested the hypothesis that acute and chronic effects of …

Neurogenesis-Mediated Forgetting Minimizes Proactive Interference., Jonathan R Epp, Rudy Silva Mera, Stefan Köhler, Sheena A Josselyn, Paul W Frankland

Brain and Mind Institute Researchers' Publications

Established memories may interfere with the encoding of new memories, particularly when existing and new memories overlap in content. By manipulating levels of hippocampal neurogenesis, here we show that neurogenesis regulates this form of proactive interference. Increasing hippocampal neurogenesis weakens existing memories and, in doing so, facilitates the encoding of new, conflicting (but not non-conflicting) information in mice. Conversely, decreasing neurogenesis stabilizes existing memories, and impedes the encoding of new, conflicting information. These results suggest that reduced proactive interference is an adaptive benefit of neurogenesis-induced forgetting.

Sensory Plasticity In Human Motor Learning., David J Ostry, Paul L Gribble

Brain and Mind Institute Researchers' Publications

There is accumulating evidence from behavioral, neurophysiological, and neuroimaging studies that the acquisition of motor skills involves both perceptual and motor learning. Perceptual learning alters movements, motor learning, and motor networks of the brain. Motor learning changes perceptual function and the sensory circuits of the brain. Here, we review studies of both human limb movement and speech that indicate that plasticity in sensory and motor systems is reciprocally linked. Taken together, this points to an approach to motor learning in which perceptual learning and sensory plasticity have a fundamental role.

Context-Dependent Egr1 Expression In The Avian Hippocampus., Stephanie L Grella, Mélanie F Guigueno, David J White, David F Sherry, Diano F Marrone

Brain and Mind Institute Researchers' Publications

In mammals, episodic memory and spatial cognition involve context-specific recruitment of unique ensembles in the hippocampal formation (HF). Despite their capacity for sophisticated spatial (e.g., for migration) and episodic-like (e.g., for food-caching) memory, the mechanisms underlying contextual representation in birds is not well understood. Here we demonstrate environment-specific Egr1 expression as male brown-headed cowbirds (Molothrus ater) navigate environments for food reward, showing that the avian HF, like its mammalian counterpart, recruits distinct neuronal ensembles to represent different contexts.

Microglia And Neurons In The Hippocampus Of Migratory Sandpipers., C G Diniz, N G M Magalhães, A A Sousa, C Santos Filho, D G Diniz, C M Lima, M A Oliveira, D C Paulo, P D C Pereira, D F Sherry, C W Picanço-Diniz

Brain and Mind Institute Researchers' Publications

The semipalmated sandpiper Calidris pusilla and the spotted sandpiper Actitis macularia are long- and short-distance migrants, respectively. C. pusilla breeds in the sub-arctic and mid-arctic tundra of Canada and Alaska and winters on the north and east coasts of South America. A. macularia breeds in a broad distribution across most of North America from the treeline to the southern United States. It winters in the southern United States, and Central and South America. The autumn migration route of C. pusilla includes a non-stop flight over the Atlantic Ocean, whereas autumn route of A. macularia is largely over land. Because of …

Behavioral, Perceptual, And Neural Alterations In Sensory And Multisensory Function In Autism Spectrum Disorder., Sarah H Baum, Ryan A Stevenson, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Although sensory processing challenges have been noted since the first clinical descriptions of autism, it has taken until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 for sensory problems to be included as part of the core symptoms of autism spectrum disorder (ASD) in the diagnostic profile. Because sensory information forms the building blocks for higher-order social and cognitive functions, we argue that sensory processing is not only an additional piece of the puzzle, but rather a critical cornerstone for characterizing and understanding ASD. In this review we discuss what …

Differential Modification Of Cortical And Thalamic Projections To Cat Primary Auditory Cortex Following Early- And Late-Onset Deafness., Nicole Chabot, Blake E Butler, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following sensory deprivation, primary somatosensory and visual cortices undergo crossmodal plasticity, which subserves the remaining modalities. However, controversy remains regarding the neuroplastic potential of primary auditory cortex (A1). To examine this, we identified cortical and thalamic projections to A1 in hearing cats and those with early- and late-onset deafness. Following early deafness, inputs from second auditory cortex (A2) are amplified, whereas the number originating in the dorsal zone (DZ) decreases. In addition, inputs from the dorsal medial geniculate nucleus (dMGN) increase, whereas those from the ventral division (vMGN) are reduced. In late-deaf cats, projections from the anterior auditory field (AAF) …

Finding The Engram., Sheena A Josselyn, Stefan Köhler, Paul W Frankland

Brain and Mind Institute Researchers' Publications

Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent 'capture' studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram.

Simulated Diabetic Ketoacidosis Therapy In Vitro Elicits Brain Cell Swelling Via Sodium-Hydrogen Exchange And Anion Transport., Keeley L Rose, Andrew J Watson, Thomas A Drysdale, Gediminas Cepinskas, Melissa Chan, C Anthony Rupar, Douglas D Fraser

Obstetrics & Gynaecology Publications

A common complication of type 1 diabetes mellitus is diabetic ketoacidosis (DKA), a state of severe insulin deficiency. A potentially harmful consequence of DKA therapy in children is cerebral edema (DKA-CE); however, the mechanisms of therapy-induced DKA-CE are unknown. Our aims were to identify the DKA treatment factors and membrane mechanisms that might contribute specifically to brain cell swelling. To this end, DKA was induced in juvenile mice with the administration of the pancreatic toxins streptozocin and alloxan. Brain slices were prepared and exposed to DKA-like conditions in vitro. Cell volume changes were imaged in response to simulated DKA therapy. …

Genomic Copy Number Variation In Mus Musculus., M Elizabeth O Locke, Maja Milojevic, Susan T Eitutis, Nisha Patel, Andrea E Wishart, Mark Daley, Kathleen A. Hill

Brain and Mind Institute Researchers' Publications

BACKGROUND: Copy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.

RESULTS: We found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of …

Long Non-Coding Rna Malat1 Regulates Hyperglycaemia Induced Inflammatory Process In The Endothelial Cells., Prasanth Puthanveetil, Shali Chen, Biao Feng, Anirudh Gautam, Subrata Chakrabarti

Pathology Publications

To examine whether the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is altered in the endothelial cells in response to glucose and the significance of such alteration. We incubated human umbilical vein endothelial cells with media containing various glucose levels. We found an increase in MALAT1 expression peaking after 12 hrs of incubation in high glucose. This increase was associated with parallel increase in serum amyloid antigen 3 (SAA3), an inflammatory ligand and target of MALAT1 and was further accompanied by increase in mRNAs and proteins of inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin …

Motor Skill Learning Between Selection And Execution., Jörn Diedrichsen, Katja Kornysheva

Brain and Mind Institute Researchers' Publications

Learning motor skills evolves from the effortful selection of single movement elements to their combined fast and accurate production. We review recent trends in the study of skill learning which suggest a hierarchical organization of the representations that underlie such expert performance, with premotor areas encoding short sequential movement elements (chunks) or particular component features (timing/spatial organization). This hierarchical representation allows the system to utilize elements of well-learned skills in a flexible manner. One neural correlate of skill development is the emergence of specialized neural circuits that can produce the required elements in a stable and invariant fashion. We discuss …

Seasonal Change In The Avian Hippocampus., David F Sherry, Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

The hippocampus plays an important role in cognitive processes, including memory and spatial orientation, in birds. The hippocampus undergoes seasonal change in food-storing birds and brood parasites, there are changes in the hippocampus during breeding, and further changes occur in some species in association with migration. In food-storing birds, seasonal change in the hippocampus occurs in fall and winter when the cognitively demanding behaviour of caching and retrieving food occurs. The timing of annual change in the hippocampus of food-storing birds is quite variable, however, and appears not to be under photoperiod control. A variety of factors, including cognitive performance, …

Attentional Filtering Of Visual Information By Neuronal Ensembles In The Primate Lateral Prefrontal Cortex., Sébastien Tremblay, Florian Pieper, Adam Sachs, Julio Martinez-Trujillo

Brain and Mind Institute Researchers' Publications

The activity of neurons in the primate lateral prefrontal cortex (LPFC) is strongly modulated by visual attention. Such a modulation has mostly been documented by averaging the activity of independently recorded neurons over repeated experimental trials. However, in realistic settings, ensembles of simultaneously active LPFC neurons must generate attentional signals on a single-trial basis, despite the individual and correlated variability of neuronal responses. Whether, under these circumstances, the LPFC can reliably generate attentional signals is unclear. Here, we show that the simultaneous activity of neuronal ensembles in the primate LPFC can be reliably decoded to predict the allocation of attention …

High-Field Functional Imaging Of Pitch Processing In Auditory Cortex Of The Cat., Blake E. Butler, Amee J Hall, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

The perception of pitch is a widely studied and hotly debated topic in human hearing. Many of these studies combine functional imaging techniques with stimuli designed to disambiguate the percept of pitch from frequency information present in the stimulus. While useful in identifying potential "pitch centres" in cortex, the existence of truly pitch-responsive neurons requires single neuron-level measures that can only be undertaken in animal models. While a number of animals have been shown to be sensitive to pitch, few studies have addressed the location of cortical generators of pitch percepts in non-human models. The current study uses high-field functional …

Prolonged In Vivo Retention Of A Cathepsin D Targeted Optical Contrast Agent In A Mouse Model Of Alzheimer's Disease., Jonatan A Snir, Mojmir Suchy, Keith St Lawrence, Robert H E Hudson, Stephen H Pasternak, Robert Bartha

Brain and Mind Institute Researchers' Publications

BACKGROUND: Cathepsin D (CatD) is a lysosomal protease that is elevated early in Alzheimer's disease (AD). We have previously developed a Targeted contrast agent (CA) to detect CatD activity in vivo, consisting of a magnetic resonance imaging/fluorescent moiety linked to a cell penetrating peptide (CPP) by means of a CatD cleavage site and have demonstrated its uptake in the brain of an AD mouse model.

OBJECTIVE: The purpose of this study was to characterize the in vivo retention of a near infra-red fluorescent dye labeled version of this CA.

METHODS: Six adult C57Bl/6 wild-type mice and six adult 5XFAD transgenic …

Low Birth Weight Followed By Postnatal Over-Nutrition In The Guinea Pig Exposes A Predominant Player In The Development Of Vascular Dysfunction., Jennifer A Thompson, Ousseynou Sarr, Karolina Piorkowska, Robert Gros, Timothy Regnault

Paediatrics Publications

The association between intrauterine growth restriction (IUGR) and hypertension is well established, yet the interaction between IUGR and other pathogenic contributors remains ill-defined. This study examined the independent and interactive effects of fetal growth reduction resulting in low birth weight (LBW), and postnatal Western diet (WD) on vascular function. Growth reduction was induced in pregnant guinea pigs by uterine artery ablation. LBW and normal birth weight (NBW) offspring were randomly assigned to a control diet (CD) or a WD. In young adulthood, length-tension curves were generated in aortic rings and responses to methacholine (MCh) were evaluated in the carotid and …

Transcranial Magnetic Stimulation Of The Prefrontal Cortex In Awake Nonhuman Primates Evokes A Polysynaptic Neck Muscle Response That Reflects Oculomotor Activity At The Time Of Stimulation., Chao Gu, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Transcranial magnetic stimulation (TMS) has emerged as an important technique in cognitive neuroscience, permitting causal inferences about the contribution of a given brain area to behavior. Despite widespread use, exactly how TMS influences neural activity throughout an interconnected network, and how such influences ultimately change behavior, remain unclear. The oculomotor system of nonhuman primates (NHPs) offers a potential animal model to bridge this gap. Here, based on results suggesting that neck muscle activity provides a sensitive indicator of oculomotor activation, we show that single pulses of TMS over the frontal eye fields (FEFs) in awake NHPs evoked rapid (within ∼25 …

Developmental Stress, Condition, And Birdsong: A Case Study In Song Sparrows., Kim L Schmidt, Elizabeth A Macdougall-Shackleton, Shawn P Kubli, Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

Sexual-selection theory posits that ornaments and displays can reflect a signaler's condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers. Here, we review data on the relationships between birdsong, a sexually selected trait, and developmental and current condition of birds from a long-term study of a population of song sparrows (Melospiza melodia). Field studies of free-living birds indicate that the …

Ct Perfusion Imaging As An Early Biomarker Of Differential Response To Stereotactic Radiosurgery In C6 Rat Gliomas, Timothy Pok Chi Yeung, Maher Kurdi, Yong Wang, Baraa Al-Khazraji, Laura Morrison, Lisa Hoffman, Dwayne Jackson, Cathie Crukley, Ting-Yim Lee, Glenn Bauman, Slav Yartsev

Medical Biophysics Publications

BACKGROUND: The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model.

METHODS: Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8) or stereotactic radiosurgery (N = 25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute …

Sharp Emergence Of Feature-Selective Sustained Activity Along The Dorsal Visual Pathway., Diego Mendoza-Halliday, Santiago Torres, Julio C Martinez-Trujillo

Brain and Mind Institute Researchers' Publications

Sustained activity encoding visual working memory representations has been observed in several cortical areas of primates. Where along the visual pathways this activity emerges remains unknown. Here we show in macaques that sustained spiking activity encoding memorized visual motion directions is absent in direction-selective neurons in early visual area middle temporal (MT). However, it is robustly present immediately downstream, in multimodal association area medial superior temporal (MST), as well as and in the lateral prefrontal cortex (LPFC). This sharp emergence of sustained activity along the dorsal visual pathway suggests a functional boundary between early visual areas, which encode sensory inputs, …

Olanzapine-Induced Methylation Alters Cadherin Gene Families And Associated Pathways Implicated In Psychosis, Melkaye G. Melka, Christina A Castellani, Nagalingam Rajakumar, Richard O'Reilly, Shiva M Singh

Biology Publications

BACKGROUND: The complex aetiology of most mental disorders involves gene-environment interactions that may operate using epigenetic mechanisms particularly DNA methylation. It may explain many of the features seen in mental disorders including transmission, expression and antipsychotic treatment responses. This report deals with the assessment of DNA methylation in response to an antipsychotic drug (olanzapine) on brain (cerebellum and hippocampus), and liver as a non-neural reference in a rat model. The study focuses on the Cadherin/protocadherins encoded by a multi-gene family that serve as adhesion molecules and are involved in cell-cell communication in the mammalian brain. A number of these molecules …