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- Title
- Hippocampal place cell activity influenced by variations of the novel object recognition task in C57BL/6J mice.
- Creator
- Asgeirsdottir, Herborg Nanna, Cohen, Sarah J., Zhang, Gongliang, Munchow, Alcira H., Stackman, Robert W., Graduate College
- Date Issued
- 2013-04-12
- PURL
- http://purl.flvc.org/fcla/dt/3361265
- Subject Headings
- Hippocampus (Brain), Neurons, Mice
- Format
- Document (PDF)
- Title
- Murine strain differences in beta-endorphin immunoreactivity.
- Creator
- Wong, Donna M., Florida Atlantic University, Lasiter, Phillip S.
- Abstract/Description
-
The murine strains BALB and C57 differ in behavioral sensitivity to opioid alkaloids, beta-endorphin, and met-/leu-enkephalin. Possible differences in levels of endogenous "opioid peptides" have not been evaluated in the BALB and C57 murine genotypes by the use of immunohistochemical procedures. Antisera to synthetic ovine beta-endorphin was used to examine neuropil and somatic immunoreactivity in various diencephalic and telencephalic areas within three strains of inbred mice, BALB/c, C57BL...
Show moreThe murine strains BALB and C57 differ in behavioral sensitivity to opioid alkaloids, beta-endorphin, and met-/leu-enkephalin. Possible differences in levels of endogenous "opioid peptides" have not been evaluated in the BALB and C57 murine genotypes by the use of immunohistochemical procedures. Antisera to synthetic ovine beta-endorphin was used to examine neuropil and somatic immunoreactivity in various diencephalic and telencephalic areas within three strains of inbred mice, BALB/c, C57BL and the heterogenous strain (CF1). Results indicate that quantitative differences exist between these strains in the number of immunoreactive cells present in the arcuate nucleus of the hypothalamus and in neuropil straining. These observations indicate that behavioral differences in opioid responsivity may relate to differences in either the number of parent somata in the arcuate nucleus and/or the organization and/or trajectory of efferent projections arising from arcuate nucleus neurons.
Show less - Date Issued
- 1988
- PURL
- http://purl.flvc.org/fcla/dt/14452
- Subject Headings
- Mice as laboratory animals, Endorphins, Mice--Immunology
- Format
- Document (PDF)
- Title
- Energy metabolism and slow skeletal troponin I phosphorylation in cardiac troponin I null mouse heart.
- Creator
- Jia, Yuanyuan, Florida Atlantic University, Huang, Xupei, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Troponin I (TnI) plays an important role in cardiac muscle contraction. Two TnI genes (cardiac and slow skeletal TnI) are predominantly expressed in the heart. In cTnI knockout mice, myocardial TnI deficiency results in a diastolic dysfunction and a sudden death in homozygous mutants. In the present studies, energy metabolism has been analyzed in myocardial cells from cTnI null hearts. Our results have demonstrated that damaged relaxation and increased Ca2+-independent force production in...
Show moreTroponin I (TnI) plays an important role in cardiac muscle contraction. Two TnI genes (cardiac and slow skeletal TnI) are predominantly expressed in the heart. In cTnI knockout mice, myocardial TnI deficiency results in a diastolic dysfunction and a sudden death in homozygous mutants. In the present studies, energy metabolism has been analyzed in myocardial cells from cTnI null hearts. Our results have demonstrated that damaged relaxation and increased Ca2+-independent force production in cTnI null hearts stimulated myofibril MgATPase activities accompanied by the increase of mitochondria quantity and ATPase activities. In addition, an increase of ssTnI phosphorylation level has been observed in cTnI null hearts. The results indicate that TnI deficiency can cause the disturbance of energy metabolism and some protein overphosphorylation.
Show less - Date Issued
- 2003
- PURL
- http://purl.flvc.org/fcla/dt/12998
- Subject Headings
- Mice as laboratory animals, Mice--Metabolism, Energy metabolism, Mitochondria
- Format
- Document (PDF)
- Title
- N-terminal truncated cardiac TnI improves cardiac function in vivo and rescues restrictive cardiomyopathy.
- Creator
- Jean-Charles, Pierre-Yves, Li, Yuejin, Nan, Changlong, Chen, Guozhen, Feng, H., Huang, Xupei, Jin, J.P., Graduate College
- Date Issued
- 2011-04-08
- PURL
- http://purl.flvc.org/fcla/dt/3164515
- Subject Headings
- Cardiac arrest, Troponin --diagnostic use, Transgenic mice
- Format
- Document (PDF)
- Title
- BRIEF EXPOSURE TO A NOVEL CONTEXT ENHANCES CONSOLIDATION OF OBJECT MEMORY IN C57BL/6J MICE.
- Creator
- Hindman, Brandon L., Stackman Jr., Robert W., Florida Atlantic University, Department of Psychology, Charles E. Schmidt College of Science
- Abstract/Description
-
Previous research revealed that episodic memories are more likely to be consolidated if something novel occurs in relative temporal proximity to the original learned event (Dunsmoor, Murty, Davachi, & Phelps, 2015). Further, research conducted with rodents has revealed that novel contextual exposure following encoding of a spatial memory in a food-motivated task results in enhanced consolidation of that spatial memory (Takeuchi, Duszkiewics, Sonneborn et al., 2016). The present study sought...
Show morePrevious research revealed that episodic memories are more likely to be consolidated if something novel occurs in relative temporal proximity to the original learned event (Dunsmoor, Murty, Davachi, & Phelps, 2015). Further, research conducted with rodents has revealed that novel contextual exposure following encoding of a spatial memory in a food-motivated task results in enhanced consolidation of that spatial memory (Takeuchi, Duszkiewics, Sonneborn et al., 2016). The present study sought to examine the influence of novel context exposure on non-spatial object memory in adult female and male C57BL/6J mice when novel context exposure follows encoding of object memory under two memory strength training protocols. Results revealed that regardless of memory strength or gender, subjects exposed to a novel context following encoding of object memory exhibited greater exploration of the novel object when assessed 23.5 h later. Thus, novel context exposure significantly enhanced the consolidation of recently encoded object memory. As novel context exposure has been shown to increase dopamine release in the hippocampus, these results are consistent with the theory of synaptic tag and capture, whereby activated dopaminergic afferents enhance the on-going consolidation of non-spatial object memory. Future studies will entail parsing potential neurotransmitter modulatory afferents via pharmacological antagonists.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013377
- Subject Headings
- Memory, Episodic memory, Neurons, Afferent, Dopamine, Mice
- Format
- Document (PDF)
- Title
- Evaluation of cardiac function in cTnI(R192H) transgenic mice and cTni knockout mice with High-Resolution Ultrasound Imaging and Doppler Echocardiography.
- Creator
- Liu, Jing, Huang, Xupei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Troponin I is a contractile protein and plays an important role in cardiac function. We have generated cTnl knockout and cTnI(R192H) transgenic mouse models. All of cTnl knockout homozygous mice die at 17-18 days after birth. Some of cTnI(R192H) transgenic mice die at early life stages, some mice develop heart failure at late stages. High-resolution ultrasound imaging and Doppler echocardiography have been used to evaluate cardiac function on cTnl deficient mice and cTnl(R192H) transgenic...
Show moreTroponin I is a contractile protein and plays an important role in cardiac function. We have generated cTnl knockout and cTnI(R192H) transgenic mouse models. All of cTnl knockout homozygous mice die at 17-18 days after birth. Some of cTnI(R192H) transgenic mice die at early life stages, some mice develop heart failure at late stages. High-resolution ultrasound imaging and Doppler echocardiography have been used to evaluate cardiac function on cTnl deficient mice and cTnl(R192H) transgenic mice. cTnI mice have damaged relaxation with gradually decreased E/A ratio(E/A<1). FS and cardiac output dramatically decrease on 17-day-o1d cTnI mice indicating severe cardiac dysfunction. We find that the damaged heart function is correspondent with the Tnl expression level decline. 6-8 weeks transgenic mice have shown that the dimension of left and right atria increase. In 15-month-old transgenic mice, the E/A ratio shows a pseudonormal pattern indicating a diastolic dysfunction. This study demonstrate that damaged heart function is tightly associated with Tnl levels in the heart.
Show less - Date Issued
- 2006
- PURL
- http://purl.flvc.org/fau/fd/FA00000789
- Subject Headings
- Transgenic mice, Mice as laboratory animals, Coronary heart disease--Seriodiagnosis, Congestive heart failure--Pathophysiology
- Format
- Document (PDF)
- Title
- In vivo administration of a subtype selective activator of small conductance Ca2+ - activated K+ channels influences hippocampal-dependent spatial memory.
- Creator
- Beck, Robert, Kuchera, Claire Rice, Munchow, Alcira H., Stackman, Robert W., Graduate College
- Date Issued
- 2013-04-12
- PURL
- http://purl.flvc.org/fcla/dt/3361271
- Subject Headings
- Calcium-dependent potassium channels, Hippocampus (Brain), Mice, Memory
- Format
- Document (PDF)
- Title
- Assessment of anatomical structures and hemodynamic function of cTnI[193His] transgenic mice with micro-echocardiography.
- Creator
- Gobara, Nariman., Charles E. Schmidt College of Medicine
- Abstract/Description
-
Transgenic mice were generated to express a restrictive cardiomyopathy (RCM) human cardiac troponin I (cTnI) R192H mutation in the heart. My study's objective was to assess cardiac function during the development of diastolic dysfunction and to gain insight into the pathophysiological impact of the RCM cTnI mutation. Cardiac function was monitored in cTnI193His mice and wild-type littermates for a period of 12 months. It progressed gradually from abnormal relaxation to diastolic dysfunction...
Show moreTransgenic mice were generated to express a restrictive cardiomyopathy (RCM) human cardiac troponin I (cTnI) R192H mutation in the heart. My study's objective was to assess cardiac function during the development of diastolic dysfunction and to gain insight into the pathophysiological impact of the RCM cTnI mutation. Cardiac function was monitored in cTnI193His mice and wild-type littermates for a period of 12 months. It progressed gradually from abnormal relaxation to diastolic dysfunction characterized with micro- echocardiography by a reversed E/A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. The negative impact of cTnI193His on cardiac function was further demonstrated in isolated mouse working heart preparations. Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO. The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation characterized morphologically by enlarged atria and restricted ventricle and functionally by diastolic dysfunction.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/186680
- Subject Headings
- Mice as laboratory animals, Biochemical markers, Diagnostic use, Cardiovascular system, Pathophysiology, Coronary heart disease, Molecular diagnosis
- Format
- Document (PDF)
- Title
- Analyses of neuronal replacement in the neuron-depleted olfactory systems in adult mice.
- Creator
- Liu, Huan, Charles E. Schmidt College of Medicine
- Abstract/Description
-
New neurons are continuously generated in the olfactory system of adult mice, including olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) and interneurons, produced in the subventricular zone (SVZ) and migrated toward olfactory bulb (OB) along rostral migratory stream (RMS). The present study observed the effects of target neuron loss on the life-span and maturation of adult-born OSNs in the OE and on the proliferation, migration and differentiation of SVZ stem cells in the...
Show moreNew neurons are continuously generated in the olfactory system of adult mice, including olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) and interneurons, produced in the subventricular zone (SVZ) and migrated toward olfactory bulb (OB) along rostral migratory stream (RMS). The present study observed the effects of target neuron loss on the life-span and maturation of adult-born OSNs in the OE and on the proliferation, migration and differentiation of SVZ stem cells in the forebrain after eliminating bulb neurons. We found the life-span of newborn neurons in the absence of synaptic targets was shortened, but the timing of maturation was not delayed. In addition, SVZ cells continued to divide and migrate to the damaged bulb, and the migration of newborn cells in the RMS on the contralateral side was delayed at 2 weeks post-BrdU. Also, the proliferation of cells in dentate gyrus of the hippocampus was not affected by OB damage at 3 weeks post-lesion, though lesion affects occurred in the adult SVZ/RMS.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/fcla/dt/172671
- Subject Headings
- Mice as laboratory animals, Neurotransmitter receptors, Sensory neurons, Testing, Cellular control mechanisms
- Format
- Document (PDF)
- Title
- CELLULAR REQUIREMENTS FOR MBLAC1 EXPRESSION AS ASSESSED IN MBLAC1-/- MOUSE EMBRYONIC FIBROBLASTS.
- Creator
- McGovern, Samantha, Blakely, Randy, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Science
- Abstract/Description
-
The majority of research on drug addiction centers on dopamine (DA)- driven synaptic plasticities and how these changes ultimately lead to compulsive drug seeking. However, growing evidence supports a role of glial factors in various steps that lead to drug abuse and addiction. In this regard, significant evidence implicates glial glutamate (Glu) transporters (GLT-1) and cystine/Glu exchangers (xCT) in determining synaptic and extrasynaptic levels of Glu that support the acute and chronic...
Show moreThe majority of research on drug addiction centers on dopamine (DA)- driven synaptic plasticities and how these changes ultimately lead to compulsive drug seeking. However, growing evidence supports a role of glial factors in various steps that lead to drug abuse and addiction. In this regard, significant evidence implicates glial glutamate (Glu) transporters (GLT-1) and cystine/Glu exchangers (xCT) in determining synaptic and extrasynaptic levels of Glu that support the acute and chronic actions of drugs of abuse. -lactam antibiotics have been found in rodent models to upregulate CNS GLT-1 and xCT and thereby contribute to reinstatement after chronic drug exposure and withdrawal. Previously, the Blakely lab identified a glial expressing gene, swip-10, in Caenorhabditis elegans, whose deletion results in the hyperdominergic phenotype Swimming-Induced Paralysis (Swip), supported by Glu signalingdependent DA neuron hyperexcitability that ultimately drives oxidative stress and DA neuron degeneration. Both SWIP-10 and its putative mammalian ortholog MBLAC1 possess a highly conserved metallo -lactamase domain, and MBLAC1 has been found to bind the Glu modulating, b-lactam antibiotic ceftriaxone (Cef). Indeed, immunodepletion studies indicate that MBLAC1 may be the major highaffinity Cef-binding protein in the brain, leading to the hypothesis that MBLAC1 has a Glu modulatory role(s). Recently a functional role of MBLAC1 been proposed, involving activity as a 3’ exonuclease that processes polyA- mRNAs, including RNAs encoding cell replication-dependent histones. How this role, or others, may support the actions of MBLAC1 in the brain and the non-microbial actions of Cef to extracellular Glu homeostasis, is unclear. Recently, the Blakely lab generated Mblac1-/- mice as a tool to investigate these issues. The following work investigated the requirements of MBLAC1 in growth and the actions of Cef in mouse embryonic fibroblasts (MEFs) cultured from either Mblac1+/+ and Mblac1-/- mice. The presented data suggested that Mblac1-/- MEFs display attenuated growth and cell proliferation relative to Mblac1+/+ MEFs. For the first time, the in vitro protective actions of Cef against oxidative stress is shown to be dependent on MBLAC1. The following studies presented contribute to a definition of the role of MBLAC1 and as a Cef binding protein in native preparations, with findings that can drive models for the role of MBLAC1 in the CNS.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013395
- Subject Headings
- Drug addiction--Research, Amino Acid Transport System X-AG, Mice, Fibroblasts
- Format
- Document (PDF)
- Title
- Influence of small conductance calcium-activated potassium channels (SK,Kca2) on long-term memory: global and local analysis across time- and task- dependent measures.
- Creator
- Vick, Kyle A., Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
-
Small conductance calcium-activated potassium (SK) channels are found ubiquitously throughout the brain and modulate the encoding of learning and memory. Systemic injection of 1-ethyl-2-benzimidalzolinoe (EBIO), a SK channel activator, impairs the encoding of novel object memory and locomotion but spares fear memory encoding in C57BL/6NHsd mice. The memory impairments discovered were not due to non-cognitive performance confounds such as ataxia, anxiety, attention or analgesia. Further...
Show moreSmall conductance calcium-activated potassium (SK) channels are found ubiquitously throughout the brain and modulate the encoding of learning and memory. Systemic injection of 1-ethyl-2-benzimidalzolinoe (EBIO), a SK channel activator, impairs the encoding of novel object memory and locomotion but spares fear memory encoding in C57BL/6NHsd mice. The memory impairments discovered were not due to non-cognitive performance confounds such as ataxia, anxiety, attention or analgesia. Further investigation with intra-hippocampal application of EBIO revealed SK channels in dorsal CA1 contribute to the encoding deficits seen systemically, but do not account for the full extent of the impairment. Concentrated activation of dorsal CA1 SK channels do not influence fear memory encoding or locomotor impairments. Taken together, these data indicate SK channels, especially in the dorsal hippocampus, have a modulatory role on novel object memory encoding, but not retrieval; however, pharmacological activation of hippocampal SK channels does not appear to influence fear memory encoding.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/192991
- Subject Headings
- Mice as laboratory animals, Cellular signal transduction, Memory, Research, Biological transport, Research, Potassium channels, Physiological effect
- Format
- Document (PDF)
- Title
- Heading in the right direction: the behavior and brain mechanisms of directional navigation.
- Creator
- Williams, Sidney Beth., Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
-
The mechanisms that rodents employ to navigate through their environment have been greatly studied. Cognitive mapping theory suggests that animals use distal cues in the environment to navigate to a goal location (place navigation). However, others have found that animals navigate in a particular direction to find a goal (directional navigation). The rodent brain contains head direction cells (HD cells) that discharge according to the head direction of the animal. Navigation by heading...
Show moreThe mechanisms that rodents employ to navigate through their environment have been greatly studied. Cognitive mapping theory suggests that animals use distal cues in the environment to navigate to a goal location (place navigation). However, others have found that animals navigate in a particular direction to find a goal (directional navigation). The rodent brain contains head direction cells (HD cells) that discharge according to the head direction of the animal. Navigation by heading direction is disrupted by lesions of the anterodorsal thalamic nuclei (ADN), many of which are HD cells. Aim 1 tested whether male C57BL/6J mice exhibit direction or place navigation in the Morris water maze. Aim 2 tested the effects of temporary inactivation of the ADN on directional navigation. Together, these data indicate that C57BL/6J mice also exhibit preference for directional navigation and suggest that the ADN may be crucial for this form of spatial navigation.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/186774
- Subject Headings
- Mice as laboratory animals, Animal navigation, Spatial behavior in animals, Cognition in animals
- Format
- Document (PDF)
- Title
- INVESTIGATING THE NEURAL CIRCUITRY SUPPORTING OBJECT RECOGNITION MEMORY IN C57BL/6J MICE.
- Creator
- Cinalli Jr., David A, Stackman, Jr., Robert W., Florida Atlantic University, Department of Psychology, Charles E. Schmidt College of Science
- Abstract/Description
-
The hippocampus, a brain region that is part of the limbic system in the medial temporal lobe, is critical to episodic memory, or the memory of autobiographical events. The hippocampus plays an important role in the consolidation of information from short-term memory into more permanent long-term memory and spatial memory which enables navigation. Hippocampal damage in humans has been linked to memory loss, such as in Alzheimer’s disease and other dementias, as well as in amnesia such as in...
Show moreThe hippocampus, a brain region that is part of the limbic system in the medial temporal lobe, is critical to episodic memory, or the memory of autobiographical events. The hippocampus plays an important role in the consolidation of information from short-term memory into more permanent long-term memory and spatial memory which enables navigation. Hippocampal damage in humans has been linked to memory loss, such as in Alzheimer’s disease and other dementias, as well as in amnesia such as in the case of patient H.M. The role of the hippocampus has been well characterized in humans but is less understood in rodents due to contradictory findings. While rodents have served well as model organisms in developing our understanding of the cognitive map that is critical for spatial navigation, there has been substantial contention over the degree to which the rodent hippocampus supports non-spatial memory, specifically the memory for items or objects previously encountered. The overall objective of this research is to gain a better understanding of how neuronal circuits involving the hippocampus and perirhinal cortex function to support object memory in the brain. Chemogenetic technologies such as DREADDs (designer receptor exclusively activated by designer drugs) have proven to be effective tools in remote manipulation of neuronal activity. First, a series of behavioral tasks was used to validate the effects of DREADD inactivation in the CA1 region of dorsal hippocampus in C57BL/6J male mice. DREADD inhibition resulted in significant impairment in the spontaneous object recognition (SOR) task and of spatial memory in the Morris water maze. In conjunction, mice were implanted with bilateral perirhinal cortex guide cannulae to allow for temporary muscimol inactivation during distinct time points in the SOR task to further investigate the nature of its relationship with the hippocampus. The results reveal an unexpected role for the perirhinal cortex in the retrieval of strong object memory. Finally, Arc mRNA expression was quantified in CA1 of dorsal hippocampus and perirhinal cortex following both weak and strong object memory formation. The results indicate that the perirhinal cortex and hippocampus have distinct, yet complementary roles in object recognition memory and that distinction is gated by memory strength. Understanding the neural mechanisms supporting the weak-strong object memory distinction in mice is an important step not only in validating mice as a suitable model system to study episodic memory in humans, but also in developing treatments and understanding the underlying causes of diseases affecting long-term memory such as Alzheimer’s disease.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013571
- Subject Headings
- Neural circuitry, Hippocampus, Perirhinal Cortex, Memory, Mice, Inbred C57BL
- Format
- Document (PDF)
- Title
- The effect of small conductance calcium-activated potassium channels on emotional learning and memory.
- Creator
- Sanguinetti, Shannon, Stackman, Robert W., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
-
Small conductance Ca2+-activated K+ (SK) channels have been shown to alter the encoding of spatial and non-spatial memory in the hippocampus by shaping glutamatergic postsynaptic potentials and modulating NMDA receptor-dependent synaptic plasticity. When activated, dendritic SK channels reduce hippocampal neuronal excitability and LTP. Similar SK channel properties have been demonstrated in lateral amygdala (LA) pyramidal neurons. Additionally, induction of synaptic plasticity and beta...
Show moreSmall conductance Ca2+-activated K+ (SK) channels have been shown to alter the encoding of spatial and non-spatial memory in the hippocampus by shaping glutamatergic postsynaptic potentials and modulating NMDA receptor-dependent synaptic plasticity. When activated, dendritic SK channels reduce hippocampal neuronal excitability and LTP. Similar SK channel properties have been demonstrated in lateral amygdala (LA) pyramidal neurons. Additionally, induction of synaptic plasticity and beta-adrenoreceptor activation in LA pyramidal neurons causes PKA-mediated internalization of SK channels from the postsynaptic density. Chronic activation of the amygdala through repetitive stressful stimuli can lead to excitatory synaptic strengthening that may create permanent hyper-excitability in its circuitry. This mechanism may contribute to a number of mood and anxiety disorders. The selective influence of SK channels in the LA on anxiety and fear conditioning are not known. The thesis project outlined herein examined whether SK channel blockade by bee venom peptide, apamin, during a repetitive acute fear conditioning paradigm was sufficient to alter fear memory encoding and the resulting behavioral outcome. Following the final fear memory test session, mice were tested in the open field immediately after the second fear conditioning test session. The findings indicate that intracranial LA microinfusions of apamin did not affect memory encoding or subsequent anxiety.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00004543, http://purl.flvc.org/fau/fd/FA00004543
- Subject Headings
- Biological transport -- Research, Cellular signal transduction, Memory -- Research, Mice as laboratory animals, Potassium channels -- Physiological effect
- Format
- Document (PDF)
- Title
- Which Way is It? Spatial Navigation and the Genetics of Head Direction Cells.
- Creator
- Lora, Joan C., Stackman, Robert W., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
-
From locating a secure home, foraging for food, running away from predators, spatial navigation is an integral part of everyday life. Multiple brain regions work together to form a three-dimensional representation of our environment; specifically, place cells, grid cells, border cells & head direction cells are thought to interact and influence one another to form this cognitive map. Head direction (HD) cells fire as the animal moves through space, according to directional orientation of the...
Show moreFrom locating a secure home, foraging for food, running away from predators, spatial navigation is an integral part of everyday life. Multiple brain regions work together to form a three-dimensional representation of our environment; specifically, place cells, grid cells, border cells & head direction cells are thought to interact and influence one another to form this cognitive map. Head direction (HD) cells fire as the animal moves through space, according to directional orientation of the animal’s head with respect to the laboratory reference frame, and are therefore considered to represent the directional sense. Interestingly, inactivation of head direction cell-containing brain regions has mixed consequences on spatial behavior. Current methods of identifying HD cells are limited to in vivo electrophysiological recordings in a dry-land environment. We first developed a dry-land version of the MWM in order to carry out behavioral-recording paired studies. Additionally, to learn about HD cells function we quantified expression of neuronal activation marker (c-Fos), and L-amino acid transporter 4 (Lat4) in neurons found within the HD cell dense anterodorsal thalamic nucleus (ADN) in mice after exploratory behavior in an open field, or forward unidirectional movement on a treadmill. We hypothesize that the degree to which ADN neurons are activated during exploratory behavior is influenced by the range of heading directions sampled. Additionally, we hypothesize that c-Fos and Lat4 are colocalized within ADN neurons following varying amounts of head direction exposure. Results indicate that following free locomotion of mice in an open field arena, which permitted access to 360° of heading, a greater number of ADN neurons express c-Fos protein compared to those exposed to a limited range of head directions during locomotion in a treadmill. These findings suggest that the degree of ADN neuronal activation was dependent upon the range of head directions sampled. We observed a high degree of colocalization of c-Fos and Lat4 within ADN suggesting that Lat4 may be a useful tool to manipulate neuronal activity of HD cells. Identifying genetic markers specific to ADN helps provide an essential understanding of the spatial navigation system, and supports development of therapies for cognitive disorders affecting navigation.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004931, http://purl.flvc.org/fau/fd/FA00004931
- Subject Headings
- Psychobiology., Spatial behavior in animals., Mice as laboratory animals., Navigation--Psychological aspects., Computational intelligence.
- Format
- Document (PDF)
- Title
- SELECTIVE MODULATION OF SMALL CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNELS IN C57BL/6J MICE RESCUES MEMORY AND ATTENTION DISORDERS IN KETAMINE-INDUCED PSYCHOSIS: A NEW THERAPEUTIC APPROACH.
- Creator
- Rice, Claire A., Stackman, Jr. Robert W., Florida Atlantic University, Department of Psychology, Charles E. Schmidt College of Science
- Abstract/Description
-
Small conductance Ca2+-activated K+ (SK) channels are expressed throughout brain regions important for long-term memory. They constrain the intrinsic excitability of neurons by enhancing afterhyperpolarization, shape glutamatergic synaptic potentials and limit induction of NMDA receptor-dependent synaptic plasticity. Behaviorally, SK channels modulate learning and memory encoding. It is hypothesized that SK channels influence cognitive symptoms of psychosis including executive functioning,...
Show moreSmall conductance Ca2+-activated K+ (SK) channels are expressed throughout brain regions important for long-term memory. They constrain the intrinsic excitability of neurons by enhancing afterhyperpolarization, shape glutamatergic synaptic potentials and limit induction of NMDA receptor-dependent synaptic plasticity. Behaviorally, SK channels modulate learning and memory encoding. It is hypothesized that SK channels influence cognitive symptoms of psychosis including executive functioning, working memory, and selective attention. Theories of psychosis currently posit that symptoms of psychosis are a result of dopaminergic hyperfunction, and glutamatergic dysregulation which can be induced following administration of the NMDA receptor antagonist, ketamine. Initial experiments confirmed that sub-chronic treatment with KET produced significant impairment of object recognition memory, trace fear memory, and latent inhibition compared to SAL mice. A comparison of ketamine dosing regimens revealed the necessity for sub-chronic/chronic dosing on a consistent schedule with a wash out period, to obtain long-lasting attention and memory impairment. These experiments revealed for the first time that sub-chronic KET treatment elicited a new phenotype in male C57BL/6J mice: audible vocalizations. KET mice emitted audible vocalizations within 10 min of receiving KET injections, and vocalizations were detected up to 30 min after injection. Experiments conducted to determine the efficacy of SK channel agonists and antagonists on SK channels to modulate attention and memory in the ketamineinduced model of psychosis in C57BL/6J mice demonstrated for the first time that the SK2 channel activator, CyPPA, significantly reduced memory impairment and decreased the attention deficit of KET mice. A new method of analysis for trace fear conditioning freezing responses permitted a more accurate measurement of the ability of mice to discriminate the predicted delivery of shock during trace versus CS intervals. The application of the novel analytical method further demonstrated that KET mice failed to accurately discriminate these intervals, due to their impaired attention and acquisition of the trace conditioned response. This study examined the efficacy of SK channel drugs to rescue cognitive impairments in a pharmacological mouse model of schizophrenia. The results indicate that SK2 subunit activators and blockers, may provide a new therapeutic treatment for memory impairment and attention deficits seen in schizophrenic disorders.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013624
- Subject Headings
- Calcium-activated potassium channels, Calcium-dependent potassium channels, Mice, Ketamine, Psychoses
- Format
- Document (PDF)
- Title
- Representation of object-in-context within mouse hippocampal neuronal activity.
- Creator
- Asgeirsdottir, Herborg Nanna, Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
-
The rodent hippocampus is critical for processing spatial memory but its contribution to non-spatial, specifically object memory is debated. The cognitive map theory of hippocampal function states that the hippocampus stores relationships of goal locations (places) to discrete items (objects) encountered within environments. Dorsal CA1 place cells were recorded in male C57BL/6J mice performing three variations of the novel object recognition paradigm to define "object-in-context"...
Show moreThe rodent hippocampus is critical for processing spatial memory but its contribution to non-spatial, specifically object memory is debated. The cognitive map theory of hippocampal function states that the hippocampus stores relationships of goal locations (places) to discrete items (objects) encountered within environments. Dorsal CA1 place cells were recorded in male C57BL/6J mice performing three variations of the novel object recognition paradigm to define "object-in-context" representation of hippocampal neuronal activity that may support object memory. Results indicate, (i) that place field stability is higher when polarizing environmental cues are provided during object recognition; (ii) hippocampal place fields remain stable throughout the novel object recognition testing without a polarizing cue; and (iii) time dependent effects on stability when objects were dissociated from the context. These data indirectly support that the rodent hippocampus processes object memory, and challenge the view that "object-in-context" representations are formed when mice perform novel object recognition task.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3362339
- Subject Headings
- Mice as laboratory animals, Hippocampus (Brain), Neurotransmitter receptors, Cellular control mechanisms, Cellular signal transduction
- Format
- Document (PDF)
- Title
- Selective Activation of the SK1 Subtype of Small Conductance Ca2+ Activated K+ Channels by GW542573X in C57BL6J Mice Impairs Hippocampal-dependent Memory.
- Creator
- Rice Kuchera, Claire A., Stackman, Robert W., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
-
SK channels are small conductance Ca2+-activated K+ channels expressed throughout the CNS. SK channels modulate the excitability of hippocampal CA1 neurons by affecting afterhyperpolarization and shaping excitatory postsynaptic responses. Such SK-mediated effects on activity-dependent neuronal excitability and synaptic strength are thought to underlie the modulatory influence of SK channels on memory encoding. Here,the effect of a new SK1 selective activator, GW542573X, on hippocampal...
Show moreSK channels are small conductance Ca2+-activated K+ channels expressed throughout the CNS. SK channels modulate the excitability of hippocampal CA1 neurons by affecting afterhyperpolarization and shaping excitatory postsynaptic responses. Such SK-mediated effects on activity-dependent neuronal excitability and synaptic strength are thought to underlie the modulatory influence of SK channels on memory encoding. Here,the effect of a new SK1 selective activator, GW542573X, on hippocampal-dependent object memory, contextual and cued conditioning, and trace fear conditioning was examined. The results demonstrated that pre- but not post-training systemic administration of GW542573X impaired object memory and trace fear memory in mice 24 h after training. Contextual and cued fear memory were not disrupted. These current data suggest that activation of SK1 subtype-containing SK channels impairs long-term memory. These results are consistent with converging evidence that SK channel activation suppressed behaviorally triggered synaptic plasticity necessary for encoding hippocampal-dependent memory.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00004541, http://purl.flvc.org/fau/fd/FA00004541
- Subject Headings
- Cellular control mechanisms, Cognitive neuroscience, Cognitive psychology, Hippocampus (Brain), Mice as laboratory animals, Neurotransmitter receptors
- Format
- Document (PDF)
- Title
- Roles of troponin I in heart development and cardiac function.
- Creator
- Du, Jianfeng., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Two major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (~1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high homology of this region among mouse, rat and human. Transfection assays indicated that conserved GA-rich sequences, CREB and a CCAAT box within the first 300 bp upstream of the transcription start site...
Show moreTwo major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (~1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high homology of this region among mouse, rat and human. Transfection assays indicated that conserved GA-rich sequences, CREB and a CCAAT box within the first 300 bp upstream of the transcription start site were critical for the gene expression. Electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays revealed binding proteins to CREB site in nuclear extracts from myocardial cells. Thyroid hormone (T3) caused a significant inhibitory effect on ssTnI expression in myocardial cells. Cardiac troponin I (cTnI) mutations have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in human cTnI Cv terminus, arginine1 92 histidine (R192H) by cardiac specific expression of the mutated protein (cTnI193His in mouse sequence) in transgenic mice. The main functional alteration detected in cTnI193His mice by ultrasound cardiac imaging examinations was impaired cardiac relaxation manifested by a decreased left ventricular end diastolic dimension (LVEDD) and an increased end diastolic dimension in both atria. Echocardiography revealed a series of changes on the transgenic mice including a reversed E-to-A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. At the age of 12 months, cardiac output in cTnI193His mice was significantly declined, and some transgenic mice showed congestive heart failure. The negative impact of cTnI193His on ventricular contraction and relaxation was further demonstrated in isolated mouse working heart preparations., Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO.The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation. The results demonstrate a critical role of the COOH-terminal domain of cTnI in the diastolic function of cardiac muscle. This mouse model provides us with a tool to further investigate the pathophysiology and the development of RCM.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/FAU/186287
- Subject Headings
- Mice as laboratory animals, Biochemical markers, Diagnostic use, Heart, Diseases, Molecular diagnosis, Cardiovascular system, Pathophysiology
- Format
- Document (PDF)
- Title
- Pathogenesis of idiopathic restrictive cardiomyopathy.
- Creator
- Li, Yuejin, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Restrictive cardiomyopathy (RCM) is a heart muscle disease, characterized by diastolic dysfunction. The present dissertation is to understand the mechanisms underlyijng the initiation of diastolic dysfunction and the fast disease progression to early death in a RCM mouse model, the transgenic cTnI193His mouse... These data showed that myocardial ischemia occurred after diastolic dysfunction and before systolic dysfunction which proceeded congestive heart failure. The results demonstrate that...
Show moreRestrictive cardiomyopathy (RCM) is a heart muscle disease, characterized by diastolic dysfunction. The present dissertation is to understand the mechanisms underlyijng the initiation of diastolic dysfunction and the fast disease progression to early death in a RCM mouse model, the transgenic cTnI193His mouse... These data showed that myocardial ischemia occurred after diastolic dysfunction and before systolic dysfunction which proceeded congestive heart failure. The results demonstrate that myocardial ischemia causing cardiomycete death is a link between the initial diastolic dysfunction and late-stage systolic dysfunction, and accelerates the disease progression to fatal heart failure in the early age.
Show less - Date Issued
- 2011
- PURL
- http://purl.flvc.org/fcla/dt/3362045
- Subject Headings
- Mice as laboratory animals, Heart conduction system, Cardiovascular system, Diseases, Genetic aspects
- Format
- Document (PDF)