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- Title
- Evidence for the emergence of relative navigational responding in male C57BL/6J mice in a land-based task.
- Creator
- Lora, Joan C., Stackman, Robert W., Graduate College
- Abstract/Description
-
We recently reported that male C57BL/6J mice navigate in spatial tasks, such as the Morris water maze MWM, by swimming in a particular direction to a location relative to poolbased cues, rather than to an absolute location defined by room-based cues. Neural mechanisms supporting this bias in rodents for relative responding rather than absolute responding in spatial tasks are not yet understood. Anterior thalamic neurons discharge according to the current directional heading of the animal. The...
Show moreWe recently reported that male C57BL/6J mice navigate in spatial tasks, such as the Morris water maze MWM, by swimming in a particular direction to a location relative to poolbased cues, rather than to an absolute location defined by room-based cues. Neural mechanisms supporting this bias in rodents for relative responding rather than absolute responding in spatial tasks are not yet understood. Anterior thalamic neurons discharge according to the current directional heading of the animal. The contribution of head direction HD cell activity to navigation has been difficult to elucidate. Selective inactivation of anterior thalamic nuclei ATN by microinfusion of muscimol or fluorophore-conjugated muscimol caused a near complete shift in preference from relative to absolute responding. Interestingly, inactivation of the dorsal CA1 region of the hippocampus did not affect relative responding. A land based version of the MWM has been developed to permit the recording of anterior thalamic HD cells during spatial search behavior. These experiments have been conducted to further examine the contribution of the HD cell activity to relative responding during spatial navigation.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00005834
- Format
- Document (PDF)
- Title
- Object-specific activity recorded from C57BL/6J mouse hippocampal CA1 neurons.
- Creator
- Asgeirsdottir, Herborg Nanna, Stackman, Robert W., Graduate College
- Abstract/Description
-
The rodent hippocampus is an essential neural substrate for spatial memory. This functional capacity is considered to rely upon a cognitive map that represents the location where relevant non-spatial items or objects are encountered and where specific events occur within a contextual or spatial reference frame. Place cell activity recorded from CA1 pyramidal neurons of the dorsal hippocampus of freely moving rodents is influenced by distal and proximal cues or items within an environment, and...
Show moreThe rodent hippocampus is an essential neural substrate for spatial memory. This functional capacity is considered to rely upon a cognitive map that represents the location where relevant non-spatial items or objects are encountered and where specific events occur within a contextual or spatial reference frame. Place cell activity recorded from CA1 pyramidal neurons of the dorsal hippocampus of freely moving rodents is influenced by distal and proximal cues or items within an environment, and increases when objects are placed into a familiar arena. Recently, the CA1 region of the rodent dorsal hippocampus was shown to play a vital role in object-in-context memory, and object memory independent of context; findings consistent with the cognitive map view. Here, we tested the influence of 3D objects on the spatial firing properties of CA1 neurons, since object-specific neuronal activity has not yet been fully established in mouse hippocampus. In vivo extracellular recordings from intermediate dorsal CA1 yielded simultaneous recordings of place cells and a pyramidal neuron demonstrating object-specific activity over two consecutive sessions with objects present. Higher frequency object-specific activity was recorded from the same mouse again 3 weeks later during a comparable task. Object-specific activity was observed only when the mouse explored objects in the arena, and was independent of spatial location or object identity. Recordings from more distal region of dorsal CA1, which receives input from proximal CA3, yielded two additional neurons that demonstrated comparable object-related activity. These results further support the involvement of the rodent hippocampus in non-spatial object memory.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00005801
- Format
- Document (PDF)
- Title
- Investigating the contribution of small conductance Ca2+ activated K+ channels to the enhancement of Pavlovian fear learning and memory through administration of apamin.
- Creator
- Sanguinetti, Shannon, Stackman, Robert W., Graduate College
- Abstract/Description
-
Chronic activation of the amygdala through repetitive stressful events can lead to permanent hyper-excitability of its circuitry, which is known to be the root of a number of mood and anxiety disorders. Small conductance Ca2+-activated K+ (SK) channels expressed on lateral amygdala (LA) pyramidal neurons shape glutamatergic postsynaptic potentials and module NMDA receptor-dependent synaptic plasticity. When activated, SK channels reduce neuronal excitability and LTP. Induction of synaptic...
Show moreChronic activation of the amygdala through repetitive stressful events can lead to permanent hyper-excitability of its circuitry, which is known to be the root of a number of mood and anxiety disorders. Small conductance Ca2+-activated K+ (SK) channels expressed on lateral amygdala (LA) pyramidal neurons shape glutamatergic postsynaptic potentials and module NMDA receptor-dependent synaptic plasticity. When activated, SK channels reduce neuronal excitability and LTP. Induction of synaptic plasticity in LA pyramidal neurons causes PKAmediated internalization of SK channels from the postsynaptic density. The current study examined whether fear conditioning would affect the subsequent sensitivity of mice to novel fear memory encoding through SK channel blockade by the bee venom peptide, apamin. Naïve male C57BL/6J mice received a systemic injection of apamin or saline prior to exposure to a 1 tone (CS) - foot shock (US) conditioning protocol. Tone fear memory strength was examined 24 hours later. The next day, mice received the same or reversed treatments of saline or apamin and were conditioned to a novel CS and context. The influence of apamin on anxiety was also examined in the elevated plus maze to determine whether the drug was able to alter anxiety independent of conditioning. The fear conditioning results suggest that prior fear conditioning altered the sensitivity of mice to apamin-induced fear memory encoding during the second conditioning session. The plus maze results indicate that solely apamin does not alter anxiety, thus fear conditioning impairment in apamin-treated mice is not a reflection of drug effects alone.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00005852
- Format
- Document (PDF)
- Title
- Selective Activation of the SK1 Subtype of Small Conductance Ca2+-Activated K+Channels by 4-(2-Methoxyphenylcarbamoyloxymethyl)-piperidine-l-carboxylic Acid tert-Butyl Ester(GW542573X) in C57BL/6J Mice lmpairs Hippocampal-Dependent Memory.
- Creator
- Kuchera, Claire Rice, Stackman, Robert W., Graduate College
- Abstract/Description
-
Small conductance Ca2+ -activated K+ (SK) channels have physiological roles in learning and memory, intrinsic excitability, synaptic transmission and plasticity, and addiction. While SK2 and SK3 channels have been studied, the role of SK1 has not yet been determined due to the prior lack of gene-specific antibodies and agonists. SK1 are robustly expressed in the CA1 pyramidal neurons of the hippocampus and modulate their excitability by affecting afterhyperpolarization. SK1 subunits are only...
Show moreSmall conductance Ca2+ -activated K+ (SK) channels have physiological roles in learning and memory, intrinsic excitability, synaptic transmission and plasticity, and addiction. While SK2 and SK3 channels have been studied, the role of SK1 has not yet been determined due to the prior lack of gene-specific antibodies and agonists. SK1 are robustly expressed in the CA1 pyramidal neurons of the hippocampus and modulate their excitability by affecting afterhyperpolarization. SK1 subunits are only sited in the plasma membrane when co-expressed with SK2 or SK3. Co-expressed and co-assembled SK1, SK2, and SK3 subunits form functional apamin-sensitive channels. SK1 are not apamin selective, suggesting the overriding hypothesis that SK1 is a subunit of heteromeric SK channels that bind specific interacting proteins. We examined the effect of a new SK1 selective activator, GW542573X, on hippocampal dependent object memory in male C57BL/6J mice. The results showed that activating SK1 channels by systemic injection of the SK1 agonist GW542573X before the sample session, led to impaired object memory in mice 24 h later. Mice treated with GW542573X acquired the sample object exploration criterion in a similar latency as the vehicle-treated mice.GW542573X treated mice exhibited significantly less preference for exploring the novel object during the test session compared to the vehicle-treated mice. These results suggest that the SK1 activator disrupted the encoding of object memory without affecting the motivation to explore objects. This supports a role for SK1 in the modulation of hippocampal synaptic plasticity and hippocampal-dependent memory.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00005830
- Format
- Document (PDF)
- Title
- The role of serotonin 5-HT2A receptors in memory and cognition.
- Creator
- Zhang, Gongliang, Stackman, Robert W.
- Date Issued
- 2015-10-06
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000190
- Format
- Citation
- Title
- Influence of voluntary exercise and environmental enrichment on long-term memory processes in C57BL/6J mice.
- Creator
- Walsh, Rebecca, Stackman, Robert W., Harriet L. Wilkes Honors College
- Abstract/Description
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Excessive fear is a hallmark of various anxiety and stress disorders, such as post-traumatic stress disorder (PTSD). Current pre-clinical research has focused on identifying behavioral and neuropharmacological methods of facilitating fear extinction in order to improve well-being of PTSD patients. The present experiment investigated the effects of voluntary exercise on fear memory and object recognition memory in male C57BL/6J mice. Results suggested that mice that exercised voluntarily...
Show moreExcessive fear is a hallmark of various anxiety and stress disorders, such as post-traumatic stress disorder (PTSD). Current pre-clinical research has focused on identifying behavioral and neuropharmacological methods of facilitating fear extinction in order to improve well-being of PTSD patients. The present experiment investigated the effects of voluntary exercise on fear memory and object recognition memory in male C57BL/6J mice. Results suggested that mice that exercised voluntarily exhibited significantly less fear-elicited freezing behavior during cued fear extinction trials compared to that of non-exercise control mice. Results from assessment of object memory revealed no difference in object memory retention between voluntary exercise mice and control mice. These results suggest that the beneficial effects of exercise in mice appear to be specific to the task and to the specific memory process. These results suggest that voluntary exercise may hold utility for remediation of PTSD and anxiety symptoms in humans.
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00003696
- 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
- Unveiling the involvement of the rodent dorsal hippocampus in object recognition memory & investigating the role of context.
- Creator
- Cohen, Sarah J., Munchow, Alcira H., Asgeirsdottir, Herborg Nanna, Stackman, Robert W., Graduate College
- Date Issued
- 2013-04-12
- PURL
- http://purl.flvc.org/fcla/dt/3361918
- Subject Headings
- Hippocampus (Brain), Rodents, Memory
- Format
- Document (PDF)
- Title
- Hippocampal involvement in object recognition memory.
- Creator
- Velez, Elisa M., Cohen, Sarah J., Stackman, Robert W.
- Date Issued
- 2013-04-05
- PURL
- http://purl.flvc.org/fcla/dt/3361221
- Subject Headings
- Hippocampus (Brain), Spatial ability
- Format
- Document (PDF)
- Title
- Effects of hippocampal impairment on rodent spatial and non-spatial memory.
- Creator
- Rios, Lisa, Lora, Joan C., Zhang, Gongliang, Stackman, Robert W., Graduate College
- Date Issued
- 2011-04-08
- PURL
- http://purl.flvc.org/fcla/dt/3164769
- Subject Headings
- Nerve Degeneration, Rodents, Space perception
- Format
- Document (PDF)
- Title
- Uncovering the role of the rodent dorsal hippocampus in object recognition memory.
- Creator
- Cohen, Sarah J., Munchow, Alcira H., Stackman, Robert W., Graduate College
- Date Issued
- 2012-03-30
- PURL
- http://purl.flvc.org/fcla/dt/3342364
- Format
- Document (PDF)
- 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
- 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
- NOVEL CONTEXT EXPOSURE ENHANCES OBJECT RECOGNITION MEMORY: ASSESSING INVOLVEMENT OF NOREPINEPHRINE NEUROTRANSMISSION.
- Creator
- Lurie, Eleonora, Stackman Jr., Robert W., Harriet L. Wilkes Honors College, Florida Atlantic University
- Abstract/Description
-
Long-term memories are encoded within the hippocampus, but some are quickly forgotten. Brief exposure of mice to a novel context following encoding of object memory significantly enhances consolidation of the object memory. The memory-enhancing effect of post-training novelty may rely on locus coeruleus tyrosine-hydroxylase expressing neurons which co-release norepinephrine and dopamine in the hippocampus. To test the contribution of norepinephrine to this novelty effect, mice received...
Show moreLong-term memories are encoded within the hippocampus, but some are quickly forgotten. Brief exposure of mice to a novel context following encoding of object memory significantly enhances consolidation of the object memory. The memory-enhancing effect of post-training novelty may rely on locus coeruleus tyrosine-hydroxylase expressing neurons which co-release norepinephrine and dopamine in the hippocampus. To test the contribution of norepinephrine to this novelty effect, mice received propranolol, a synthetic beta-adrenergic receptor antagonist (10 mg/kg), to block norepinephrine or 0.9% saline as a control post-training. Pre-novel context exposure and object memory was tested 24 hr later. Results revealed that propranolol did not block the memory enhancing effect of post-training novel context exposure. Further, the memory performance of the propranolol-treated mice was comparable to that of saline-treated mice. These findings support the view that enhanced consolidation of object memory brought about by post-training novel context exposure is not dependent upon norepinephrine neurotransmission.
Show less - Date Issued
- 2022
- PURL
- http://purl.flvc.org/fau/fd/FAUHT00240
- Format
- Document (PDF)
- Title
- Behavioral and Electrophysiological Evidence for Hippocampal Involvement in Object Motion Processing in C57BL/6J Mice.
- Creator
- Asgeirsdottir, Herborg Nanna, Stackman, Robert W., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
-
Considerable research has been carried out to establish a rodent model for the study of human memory, yet functional similarities between the species remain up for debate. The hippocampus, a region deep within the medial temporal lobe of the mammalian CNS, is critical for long-term episodic memory. Projections from the medial entorhinal cortex convey spatial/contextual information, while projections from the lateral entorhinal cortex convey item/object information to the hippocampus. The...
Show moreConsiderable research has been carried out to establish a rodent model for the study of human memory, yet functional similarities between the species remain up for debate. The hippocampus, a region deep within the medial temporal lobe of the mammalian CNS, is critical for long-term episodic memory. Projections from the medial entorhinal cortex convey spatial/contextual information, while projections from the lateral entorhinal cortex convey item/object information to the hippocampus. The functional significance of these parallel projections to the rodent hippocampus has been suggested to support spatial processing, while the same projections to the human hippocampus support spatial and non-spatial memory. Discharging in a location-specific manner, hippocampal place cells contribute to spatial memory; however, evidence for neuronal correlates of non-spatial object memory has not been fully defined. The current experiments were designed to address the following questions, while utilizing electrophysiology, functional inactivation during a novel behavioral task, and immunohistochemistry. Is the memory for objects hippocampal-dependent, solely due to the location of the object, or are objects represented within hippocampal activity independent of location? To tease apart spatial and non-spatial processing by the hippocampus, the spatial aspects of 3D objects were enhanced by utilizing movement. A novel discriminatory avoidance task, Knowing Your Enemy, was adapted from an Enemy Avoidance task to test true object memory in mice. Current findings support the notion that object-associations acquisition depends upon a specific context. Retrieval of such object-associations is not context-dependent, yet remains sensitive to temporary inactivation of the CA1 region of the dorsal hippocampus. The avoidance impairments observed following hippocampal inactivation were shown to not be a result of reduced anxiety. Immunohistochemical marker expression suggests that the CA1 region was highly active during object exposures, yet the hippocampal system responded differentially to moving and to stationary objects. Recordings of CA1 neurons yielded non-bursting object-related activity during object exploration, and place cell activity remained unaffected in the presence of moving objects; supporting independent, yet simultaneous processing of spatial and non-spatial information within the hippocampus. Together, the current findings support the notion that the CA1 region of the rodent hippocampus processes object-related information, independent of spatial information.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004981
- Subject Headings
- Dissertations, Academic -- Florida Atlantic University, Hippocampus (Brain), Declarative memory, Explicit memory.
- 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
- 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
- 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
- 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
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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)