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NOVEL CONTEXT EXPOSURE ENHANCES OBJECT RECOGNITION MEMORY: ASSESSING INVOLVEMENT OF NOREPINEPHRINE NEUROTRANSMISSION
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.
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Date Issued
2022
PURL
http://purl.flvc.org/fau/fd/FAUHT00240
Format
Document (PDF)
INVESTIGATING THE NEURAL CIRCUITRY SUPPORTING OBJECT RECOGNITION MEMORY IN C57BL/6J MICE
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.
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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)
BRIEF EXPOSURE TO A NOVEL CONTEXT ENHANCES CONSOLIDATION OF OBJECT MEMORY IN C57BL/6J MICE
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.
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Date Issued
2019
PURL
http://purl.flvc.org/fau/fd/FA00013377
Subject Headings
Memory, Episodic memory, Neurons, Afferent, Dopamine, Mice
Format
Document (PDF)
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
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.
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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)
THE EFFECTS OF AUTISM-ASSOCIATED TBR1 HAPLOINSUFFICIENCY ON AMYGDALA MORPHOLOGICAL AND FUNCTIONAL CONNECTIVITY
Title
THE EFFECTS OF AUTISM-ASSOCIATED TBR1 HAPLOINSUFFICIENCY ON AMYGDALA MORPHOLOGICAL AND FUNCTIONAL CONNECTIVITY.
Creator
Asbeck, Ingo, Bolton, M. McLean, Stackman Jr., Robert W., Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that effects about 1 in 44 children and has steadily increased in prevalence over the last decades. ASD is characterized by the diagnostic criteria of a persistent deficit in social communication and interaction and restricted or repetitive behaviors. The amygdala plays an essential role in regulating these behaviors and has continuously been shown to be affected in patients with ASD. As the amygdala is connected throughout the...
Show moreAutism spectrum disorder (ASD) is a neurodevelopmental disorder that effects about 1 in 44 children and has steadily increased in prevalence over the last decades. ASD is characterized by the diagnostic criteria of a persistent deficit in social communication and interaction and restricted or repetitive behaviors. The amygdala plays an essential role in regulating these behaviors and has continuously been shown to be affected in patients with ASD. As the amygdala is connected throughout the brain with cortical and subcortical areas, it is crucial to understand potential circuit impairments that contribute to the development and progression of behavioral characteristics. In this study, we investigated the role of ASD-associated TBR1 haploinsufficiency on morphological and functional amygdala connectivity. While we don’t see differences in inputs to the basal amygdala (BA), we demonstrated a difference in the BA to prefrontal cortex (PFC) pathway. Interestingly, we show a specific innervation difference of layer 5 neurons in the infralimbic (IL) but not prelimbic (PL) nuclei in the PFC. In accordance with the overall reduced density of BA axons in the IL, we show a decreased density of excitatory synapses. To investigate possible functional consequences of this projection deficit, we characterized pre-and postsynaptic functions of BA-PFC synapses. TBR1 haploinsufficiency impairs the postsynaptic function of BA-PL layer 2/3 and IL layer 5 synapses. BA-PL layer 2/3 synapses show an increased AMPA/NMDA receptor ratio, while this is not observed in BA-IL layer 5 synapses. However, TBR1 haploinsufficiency increases the AMPA and NMDA receptor-mediated currents at these synapses, further highlighting that BA-PL and BA-IL synapses are different and that partial loss of TBR1 affects circuits differently. This novel characterization of the consequences of a TBR1 haploinsufficiency on BA connectivity contributes to the critical understanding of this ASD-associated gene and its detrimental effects that contribute to the underlying behavioral phenotype.
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Date Issued
2022
PURL
http://purl.flvc.org/fau/fd/FA00014067
Subject Headings
Autism Spectrum Disorder, Amygdala, Haploinsufficiency
Format
Document (PDF)
HEAD DIRECTION CELL NETWORK AND SPATIAL NAVIGATION: EFFECTS OF SILENCING ANTERODORSAL THALAMIC NEURONS USING DREADDS
Title
HEAD DIRECTION CELL NETWORK AND SPATIAL NAVIGATION: EFFECTS OF SILENCING ANTERODORSAL THALAMIC NEURONS USING DREADDS.
Creator
Crafton, Brittany Nicole, Stackman Jr., Robert W., Florida Atlantic University, Department of Psychology, Charles E. Schmidt College of Science
Abstract/Description
While the thalamus and hippocampus are generally understood to contribute to mammalian spatial navigation, the degree to which thalamic input contributes to representations of space during navigation remains unclear. Specifically, anterior dorsal thalamic nuclei (ADN) provide a relational or directional framework known as the head direction (HD) network, which is hypothesized to play a significant role in guiding hippocampal-dependent navigation. The current study focuses on the contribution...
Show moreWhile the thalamus and hippocampus are generally understood to contribute to mammalian spatial navigation, the degree to which thalamic input contributes to representations of space during navigation remains unclear. Specifically, anterior dorsal thalamic nuclei (ADN) provide a relational or directional framework known as the head direction (HD) network, which is hypothesized to play a significant role in guiding hippocampal-dependent navigation. The current study focuses on the contribution of the ADN to direction and place-dependent spatial navigation in adult male C57BL6J mice. An inhibitory chemogenetic (hM4Di) receptor was bilaterally expressed in the ADN after viral stereotaxic injection. Mice were trained in a spatially focused task, the Morris water maze (MWM), and after systemic administration of the hM4Di agonist, clozapine-Noxide (CNO) at 5mg/kg, demonstrated equivalent preference for using directional or place-based search behavior. These results suggest that the selective silencing of ADN at 5mg/kg CNO does not negatively affect spatial navigation in mice.
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Date Issued
2023
PURL
http://purl.flvc.org/fau/fd/FA00014247
Subject Headings
Spatial Navigation, Anterior Thalamic Nuclei, Spatial Memory
Format
Document (PDF)