Christa McIntyre - Academia.edu (original) (raw)

Papers by Christa McIntyre

Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD), and the t... more Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD), and the two conditions are referred to as "signature wounds" of veterans returning from conflicts. PTSD and TBI show overlap clinically and symptomatically and meta-analyses show significant overlap in the neural circuitry involved in the two conditions. We propose to test the effect of brain injury on the development and treatment of PTSD symptoms and extinction impairment. Using a rat model of PTSD with prolonged and severe trauma, as well as precise and controlled lesions of regions of the brain that are involved in extinction of conditioned fear such as the prefrontal cortex, the present study aims to investigate whether VNS administration during extinction training may enhance extinction of conditioned fear in brain-injured rats.

Systems, methods and devices for paired training include timing controls so that training and neu... more Systems, methods and devices for paired training include timing controls so that training and neural stimulation can be provided simultaneously. Paired trainings may include therapies, rehabilitation and performance enhancement training. Stimulations of nerves such as the vagus nerve that affect subcortical regions such as the nucleus basalis, locus coeruleus or amygdala induce plasticity in the brain, enhancing the effects of a variety of therapies, such as those used to treat tinnitus, stroke, traumatic brain injury and post-traumatic stress disorder.

Systems, methods and devices for paired training include timing controls so that training and neu... more Systems, methods and devices for paired training include timing controls so that training and neural stimulation can be provided simultaneously. Paired trainings may include therapies, rehabilitation and performance enhancement training. Stimulations of nerves such as the vagus nerve that affect subcortical regions such as the nucleus basalis, locus coeruleus or amygdala induce plasticity in the brain, enhancing the effects of a variety of therapies, such as those used to treat tinnitus, stroke, traumatic brain injury and post-traumatic stress disorder.

The effects of vagus nerve stimulation in a rat model of PTSD

doi: 10.3389/fnbeh.2014.00091 A phosphodiesterase 4-controlled switch between memory extinction a... more doi: 10.3389/fnbeh.2014.00091 A phosphodiesterase 4-controlled switch between memory extinction and strengthening in the hippocampus

Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance ... more Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance in rats

Frontiers in Behavioral Neuroscience, 2021

Post-traumatic stress disorder (PTSD) is associated with decreased activity in the prefrontal cor... more Post-traumatic stress disorder (PTSD) is associated with decreased activity in the prefrontal cortex. PTSD-like pathophysiology and behaviors have been observed in rodents exposed to a single prolonged stress (SPS) procedure. When animals are left alone for 7 days after SPS treatment, they show increased anxiety-like behavior and impaired extinction of conditioned fear, and reduced activity in the prefrontal cortex. Here, we tested the hypothesis that daily optogenetic stimulation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) during the 7 days after SPS would reverse SPS effects on anxiety and fear extinction. Male Sprague-Dawley rats underwent SPS and then received daily optogenetic stimulation (20 Hz, 2 s trains, every 10 s for 15 min/day) of glutamatergic neurons of the left or right IL for seven days. After this incubation period, rats were tested in the elevated plus-maze (EPM). Twenty-four hours after the EPM test, rats underwent auditory fear condition...

Neurobiology of Learning and Memory, 2021

Traumatic experiences involve complex sensory information, and individuals with trauma-related ps... more Traumatic experiences involve complex sensory information, and individuals with trauma-related psychological disorders, such as posttraumatic stress disorder (PTSD), can exhibit abnormal fear to numerous different stimuli that remind them of the trauma. Vagus nerve stimulation (VNS) enhances extinction of auditory fear conditioning in rat models for PTSD. We recently found that VNS-paired extinction can also promote extinction generalization across different auditory cues. Here we tested whether VNS can enhance extinction of olfactory fear and promote extinction generalization across auditory and olfactory sensory modalities. Male Sprague Dawley rats were implanted with a stimulating cuff on the cervical vagus nerve. Rats then received two days of fear conditioning where olfactory (amyl acetate odor) and auditory (9 kHz tones) stimuli were concomitantly paired with footshock. Twenty-four hours later, the rats were given three days of sham or VNS-paired extinction (5 stimulations, 30-sec trains at 0.4 mA) overlapping with presentation of either the olfactory or the auditory stimulus. Two days later, rats were given an extinction retention test where avoidance of the olfactory stimulus or freezing to the auditory stimulus were measured. VNS-paired with exposure to the olfactory stimulus during extinction reduced avoidance of the odor in the retention test. VNS-paired with exposure to the auditory stimulus during extinction also decreased avoidance of the olfactory cue, and VNS paired with exposure to the olfactory stimulus during extinction reduced freezing when the auditory stimulus was presented in the retention test. These results indicate that VNS enhances extinction of olfactory fear and promotes extinction generalization across different sensory modalities. Extinction generalization induced by VNS may therefore improve outcomes of exposure-based therapies.

Learning & Memory, 2019

Vagus nerve stimulation (VNS) enhances extinction of conditioned fear in rats. Previous findings ... more Vagus nerve stimulation (VNS) enhances extinction of conditioned fear in rats. Previous findings support the hypothesis that VNS effects on extinction are due to enhanced consolidation of extinction memories through promotion of plasticity in extinction-related brain pathways however, alternative explanations are plausible. According to one hypothesis, VNS may produce a hedonic effect and enhance extinction through counter-conditioning. According to another hypothesis, VNS reduces anxiety during exposure and this weakens the association of conditioned stimuli with aversive conditioned responses. The present set of experiments (1) used conditioned place preference (CPP) to identify potential rewarding effects associated with VNS and (2) examined the peripheral effects of VNS on anxiety and extinction enhancement. Male Sprague–Dawley rats were surgically implanted with cuff electrodes around the vagus nerve and subjected to a CPP task in which VNS and sham stimulation were each paired...

Frontiers in Pharmacology, 2017

The endurance of memories of emotionally arousing events serves the adaptive role of minimizing f... more The endurance of memories of emotionally arousing events serves the adaptive role of minimizing future exposure to danger and reinforcing rewarding behaviors. However, following a traumatic event, a subset of individuals suffers from persistent pathological symptoms such as those seen in posttraumatic stress disorder (PTSD). Despite the availability of pharmacological treatments and evidence-based cognitive behavioral therapy, a considerable number of PTSD patients do not respond to the treatment, or show partial remission and relapse of the symptoms. In controlled laboratory studies, PTSD patients show deficient ability to extinguish conditioned fear. Failure to extinguish learned fear could be responsible for the persistence of PTSD symptoms such as elevated anxiety, arousal, and avoidance. It may also explain the high non-response and dropout rates seen during treatment. Animal models are useful for understanding the pathophysiology of the disorder and the development of new treatments. This review examines studies in a rodent model of PTSD with the goal of identifying behavioral and physiological factors that predispose individuals to PTSD symptoms. Single prolonged stress (SPS) is a frequently used rat model of PTSD that involves exposure to several successive stressors. SPS rats show PTSD-like symptoms, including impaired extinction of conditioned fear. Since its development by the Liberzon lab in 1997, the SPS model has been referred to by more than 200 published papers. Here we consider the findings of these studies and unresolved questions that may be investigated using the model.

Frontiers in Neuroscience, 2007

ABSTRACT Emotionally significant experiences tend to be well remembered.1,2 We know this from per... more ABSTRACT Emotionally significant experiences tend to be well remembered.1,2 We know this from personal experiences as well as from extensive research findings. Significant experiences such as birthdays, graduation ceremonies, or the loss of a loved one typically leave lasting and vivid memories. Findings of experimental studies indicate that people have good recollections of where they were and what they were doing when they experienced earthquakes3 or witnessed accidents.4 Similarly, a rat remembers the place in an apparatus where it received a footshock or the location of an escape platform in a tank filled with water.5,6 Such memory enhancement is not limited to experiences that are unpleasant or aversive. Pleasurable events also tend to be well remembered. Our research focuses on understanding the role of emotional responses induced by such arousing experiences in enabling the significance of events to regulate their remembrance. Extensive evidence indicates that stress hormones released from the adrenal glands are critically involved in memory consolidation of emotionally arousing experiences. Epinephrine, glucocorticoids, and specific agonists for their receptors administered after exposure to emotionally arousing experiences enhance the consolidation of long-term memories of these experiences.7–10 Do stress hormones also enhance memories of experiences that are not emotionally arousing? The findings of recent experiments suggest that this may not be the case. As discussed below, we recently reported that the endogenous glucocorticoid corticosterone enhanced memory consolidation of object recognition training when administered to rats that were emotionally aroused by an unfamiliar training apparatus. However, the treatment had no effect when administered to rats that had extensive prior habituation to the training context in order to reduce novelty-induced arousal.11 In studies of human memory, epinephrine or cortisol treatment also appear to selectively enhance memory for emotionally arousing material.12–15 These findings thus provide some important clues concerning the neurobiological mechanism(s) underlying adrenal hormone effects on memory consolidation and suggest that at least some degree of training-associated endogenous emotional arousal is essential for enabling their effects on memory consolidation. Our findings indicate that adrenal stress hormones influence memory consolidation of emotional experiences via interactions with arousal-induced activation of noradrenergic mechanisms within the amygdala.

Reviews in the Neurosciences, 2012

Acute stress and emotional arousal can enhance the consolidation of long-term memories in a manne... more Acute stress and emotional arousal can enhance the consolidation of long-term memories in a manner that is dependent on β-adrenoceptor activation in the basolateral complex of the amygdala (BLA). The BLA interacts with multiple memory systems in the brain to modulate a variety of classes of memory. However, the synaptic mechanisms of this interaction remain unresolved. This review describes the evidence of modulation of memory and synaptic plasticity produced by emotional arousal, stress hormones, and pharmacological or electrophysiological stimulation of the amygdala. The amygdala modulation of local translation and/or degradation of the synaptic plasticity-related proteins, activity-regulated cytoskeletal-associated protein and calcium/calmodulindependent protein kinase II α , is offered as a potential mechanism for the rapid memory consolidation that is associated with emotionally arousing events. This model shares features with synaptic tagging and the emotional tagging hypotheses.

Behavioural Pharmacology, 2003

Muscarinic cholinergic activation is a critical component of basolateral amygdala (BLA)-mediated ... more Muscarinic cholinergic activation is a critical component of basolateral amygdala (BLA)-mediated modulation of memory consolidation. The receptor(s) mediating this activation during consolidation have not been elucidated. This study investigated the roles of muscarinic subtype 1 (m1) and subtype 2 (m2) receptors in memory enhancement, by post-training intra-BLA infusions of the nonselective muscarinic agonist oxotremorine. Rats received intra-BLA infusions of either oxotremorine alone (10 lg in 0.2 ll per side), oxotremorine together with the selective m1 antagonist telenzipine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine with the selective m2 antagonist methoctramine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine with a combination of the above doses of telenzipine and methoctramine, or only vehicle, immediately after inhibitory avoidance training. Performance on a 48-hour retention test was significantly enhanced in oxotremorine-treated rats relative to vehicle-infused controls. Intra-BLA coinfusion of oxotremorine with either telenzipine (5, 17 or 50 nmol/side) or methoctramine (17 or 50 nmol/side) blocked the oxotremorine-induced enhancement. Combinations of these antagonists did not act additively to block memory enhancement by oxotremorine. These findings indicate that modulation of memory consolidation induced by cholinergic influences within the BLA requires activation of both m1 and m2 receptor synapses. Plausible mechanisms for m1-and m2-mediated influences on BLA circuitry are discussed.

Memory consolidation: Essays in honor of James L. McGaugh., 2001

Cognitive Behaviour Therapy, 2015

Brain-derived neurotrophic factor (BDNF) is associated with synaptic plasticity, which is crucial... more Brain-derived neurotrophic factor (BDNF) is associated with synaptic plasticity, which is crucial for long-term learning and memory. Some studies suggest that people suffering from anxiety disorders show reduced BDNF relative to healthy controls. Lower BDNF is associated with impaired learning, cognitive deficits, and poor exposure-based treatment outcomes. A series of studies with rats showed that exercise elevates BDNF and enhances fear extinction. However, this strategy has not been tested in humans. In this pilot study, we randomized participants (N = 9, 8 females, M Age = 34) with posttraumatic stress disorder (PTSD) to (a) prolonged exposure alone (PE) or (b) prolonged exposure + exercise (PE + E). Participants randomized to the PE + E condition completed a 30-minute bout of moderate-intensity treadmill exercise (70% of agepredicted HR max) prior to each PE session. Consistent with prediction, the PE + E group showed a greater improvement in PTSD symptoms (d = 2.65) and elevated BDNF (d = 1.08) relative to the PE only condition. This pilot study provides initial support for further investigation into exercise augmented exposure therapy.

Frontiers in Pharmacology, 2017

High levels of emotional arousal can impair spatial memory mediated by the hippocampus, and enhan... more High levels of emotional arousal can impair spatial memory mediated by the hippocampus, and enhance stimulus-response (S-R) habit memory mediated by the dorsolateral striatum (DLS). The present study was conducted to determine whether these memory systems may be similarly affected in an animal model of post-traumatic stress disorder (PTSD). Sprague-Dawley rats were subjected to a "single-prolonged stress" (SPS) procedure and 1 week later received training in one of two distinct versions of the plus-maze: a hippocampus-dependent place learning task or a DLS-dependent response learning task. Results indicated that, relative to non-stressed control rats, SPS rats displayed slower acquisition in the place learning task and faster acquisition in the response learning task. In addition, extinction of place learning and response learning was impaired in rats exposed to SPS, relative to non-stressed controls. The influence of SPS on hippocampal spatial memory and DLS habit memory observed in the present study may be relevant to understanding some common features of PTSD, including hippocampal memory deficits, habit-like avoidance responses to trauma-related stimuli, and greater likelihood of developing drug addiction and alcoholism.

Frontiers in Behavioral Neuroscience

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by experiencing or wi... more Posttraumatic stress disorder (PTSD) is a mental health condition triggered by experiencing or witnessing a terrifying event that can lead to lifelong burden that increases mortality and adverse health outcomes. Yet, no new treatments have reached the market in two decades. Thus, screening potential interventions for PTSD is of high priority. Animal models often serve as a critical translational tool to bring new therapeutics from bench to bedside. However, the lack of concordance of some human clinical trial outcomes with preclinical animal efficacy findings has led to a questioning of the methods of how animal studies are conducted and translational validity established. Thus, we conducted a systematic review to determine methodological variability in studies that applied a prominent animal model of trauma-like stress, single prolonged stress (SPS). The SPS model has been utilized to evaluate a myriad of PTSD-relevant outcomes including extinction retention. Rodents exposed to SPS...

Bioelectronics in Medicine

Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD), and the t... more Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD), and the two conditions are referred to as "signature wounds" of veterans returning from conflicts. PTSD and TBI show overlap clinically and symptomatically and meta-analyses show significant overlap in the neural circuitry involved in the two conditions. We propose to test the effect of brain injury on the development and treatment of PTSD symptoms and extinction impairment. Using a rat model of PTSD with prolonged and severe trauma, as well as precise and controlled lesions of regions of the brain that are involved in extinction of conditioned fear such as the prefrontal cortex, the present study aims to investigate whether VNS administration during extinction training may enhance extinction of conditioned fear in brain-injured rats.

Systems, methods and devices for paired training include timing controls so that training and neu... more Systems, methods and devices for paired training include timing controls so that training and neural stimulation can be provided simultaneously. Paired trainings may include therapies, rehabilitation and performance enhancement training. Stimulations of nerves such as the vagus nerve that affect subcortical regions such as the nucleus basalis, locus coeruleus or amygdala induce plasticity in the brain, enhancing the effects of a variety of therapies, such as those used to treat tinnitus, stroke, traumatic brain injury and post-traumatic stress disorder.

Systems, methods and devices for paired training include timing controls so that training and neu... more Systems, methods and devices for paired training include timing controls so that training and neural stimulation can be provided simultaneously. Paired trainings may include therapies, rehabilitation and performance enhancement training. Stimulations of nerves such as the vagus nerve that affect subcortical regions such as the nucleus basalis, locus coeruleus or amygdala induce plasticity in the brain, enhancing the effects of a variety of therapies, such as those used to treat tinnitus, stroke, traumatic brain injury and post-traumatic stress disorder.

The effects of vagus nerve stimulation in a rat model of PTSD

doi: 10.3389/fnbeh.2014.00091 A phosphodiesterase 4-controlled switch between memory extinction a... more doi: 10.3389/fnbeh.2014.00091 A phosphodiesterase 4-controlled switch between memory extinction and strengthening in the hippocampus

Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance ... more Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance in rats

Frontiers in Behavioral Neuroscience, 2021

Post-traumatic stress disorder (PTSD) is associated with decreased activity in the prefrontal cor... more Post-traumatic stress disorder (PTSD) is associated with decreased activity in the prefrontal cortex. PTSD-like pathophysiology and behaviors have been observed in rodents exposed to a single prolonged stress (SPS) procedure. When animals are left alone for 7 days after SPS treatment, they show increased anxiety-like behavior and impaired extinction of conditioned fear, and reduced activity in the prefrontal cortex. Here, we tested the hypothesis that daily optogenetic stimulation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) during the 7 days after SPS would reverse SPS effects on anxiety and fear extinction. Male Sprague-Dawley rats underwent SPS and then received daily optogenetic stimulation (20 Hz, 2 s trains, every 10 s for 15 min/day) of glutamatergic neurons of the left or right IL for seven days. After this incubation period, rats were tested in the elevated plus-maze (EPM). Twenty-four hours after the EPM test, rats underwent auditory fear condition...

Neurobiology of Learning and Memory, 2021

Traumatic experiences involve complex sensory information, and individuals with trauma-related ps... more Traumatic experiences involve complex sensory information, and individuals with trauma-related psychological disorders, such as posttraumatic stress disorder (PTSD), can exhibit abnormal fear to numerous different stimuli that remind them of the trauma. Vagus nerve stimulation (VNS) enhances extinction of auditory fear conditioning in rat models for PTSD. We recently found that VNS-paired extinction can also promote extinction generalization across different auditory cues. Here we tested whether VNS can enhance extinction of olfactory fear and promote extinction generalization across auditory and olfactory sensory modalities. Male Sprague Dawley rats were implanted with a stimulating cuff on the cervical vagus nerve. Rats then received two days of fear conditioning where olfactory (amyl acetate odor) and auditory (9 kHz tones) stimuli were concomitantly paired with footshock. Twenty-four hours later, the rats were given three days of sham or VNS-paired extinction (5 stimulations, 30-sec trains at 0.4 mA) overlapping with presentation of either the olfactory or the auditory stimulus. Two days later, rats were given an extinction retention test where avoidance of the olfactory stimulus or freezing to the auditory stimulus were measured. VNS-paired with exposure to the olfactory stimulus during extinction reduced avoidance of the odor in the retention test. VNS-paired with exposure to the auditory stimulus during extinction also decreased avoidance of the olfactory cue, and VNS paired with exposure to the olfactory stimulus during extinction reduced freezing when the auditory stimulus was presented in the retention test. These results indicate that VNS enhances extinction of olfactory fear and promotes extinction generalization across different sensory modalities. Extinction generalization induced by VNS may therefore improve outcomes of exposure-based therapies.

Learning & Memory, 2019

Vagus nerve stimulation (VNS) enhances extinction of conditioned fear in rats. Previous findings ... more Vagus nerve stimulation (VNS) enhances extinction of conditioned fear in rats. Previous findings support the hypothesis that VNS effects on extinction are due to enhanced consolidation of extinction memories through promotion of plasticity in extinction-related brain pathways however, alternative explanations are plausible. According to one hypothesis, VNS may produce a hedonic effect and enhance extinction through counter-conditioning. According to another hypothesis, VNS reduces anxiety during exposure and this weakens the association of conditioned stimuli with aversive conditioned responses. The present set of experiments (1) used conditioned place preference (CPP) to identify potential rewarding effects associated with VNS and (2) examined the peripheral effects of VNS on anxiety and extinction enhancement. Male Sprague–Dawley rats were surgically implanted with cuff electrodes around the vagus nerve and subjected to a CPP task in which VNS and sham stimulation were each paired...

Frontiers in Pharmacology, 2017

The endurance of memories of emotionally arousing events serves the adaptive role of minimizing f... more The endurance of memories of emotionally arousing events serves the adaptive role of minimizing future exposure to danger and reinforcing rewarding behaviors. However, following a traumatic event, a subset of individuals suffers from persistent pathological symptoms such as those seen in posttraumatic stress disorder (PTSD). Despite the availability of pharmacological treatments and evidence-based cognitive behavioral therapy, a considerable number of PTSD patients do not respond to the treatment, or show partial remission and relapse of the symptoms. In controlled laboratory studies, PTSD patients show deficient ability to extinguish conditioned fear. Failure to extinguish learned fear could be responsible for the persistence of PTSD symptoms such as elevated anxiety, arousal, and avoidance. It may also explain the high non-response and dropout rates seen during treatment. Animal models are useful for understanding the pathophysiology of the disorder and the development of new treatments. This review examines studies in a rodent model of PTSD with the goal of identifying behavioral and physiological factors that predispose individuals to PTSD symptoms. Single prolonged stress (SPS) is a frequently used rat model of PTSD that involves exposure to several successive stressors. SPS rats show PTSD-like symptoms, including impaired extinction of conditioned fear. Since its development by the Liberzon lab in 1997, the SPS model has been referred to by more than 200 published papers. Here we consider the findings of these studies and unresolved questions that may be investigated using the model.

Frontiers in Neuroscience, 2007

ABSTRACT Emotionally significant experiences tend to be well remembered.1,2 We know this from per... more ABSTRACT Emotionally significant experiences tend to be well remembered.1,2 We know this from personal experiences as well as from extensive research findings. Significant experiences such as birthdays, graduation ceremonies, or the loss of a loved one typically leave lasting and vivid memories. Findings of experimental studies indicate that people have good recollections of where they were and what they were doing when they experienced earthquakes3 or witnessed accidents.4 Similarly, a rat remembers the place in an apparatus where it received a footshock or the location of an escape platform in a tank filled with water.5,6 Such memory enhancement is not limited to experiences that are unpleasant or aversive. Pleasurable events also tend to be well remembered. Our research focuses on understanding the role of emotional responses induced by such arousing experiences in enabling the significance of events to regulate their remembrance. Extensive evidence indicates that stress hormones released from the adrenal glands are critically involved in memory consolidation of emotionally arousing experiences. Epinephrine, glucocorticoids, and specific agonists for their receptors administered after exposure to emotionally arousing experiences enhance the consolidation of long-term memories of these experiences.7–10 Do stress hormones also enhance memories of experiences that are not emotionally arousing? The findings of recent experiments suggest that this may not be the case. As discussed below, we recently reported that the endogenous glucocorticoid corticosterone enhanced memory consolidation of object recognition training when administered to rats that were emotionally aroused by an unfamiliar training apparatus. However, the treatment had no effect when administered to rats that had extensive prior habituation to the training context in order to reduce novelty-induced arousal.11 In studies of human memory, epinephrine or cortisol treatment also appear to selectively enhance memory for emotionally arousing material.12–15 These findings thus provide some important clues concerning the neurobiological mechanism(s) underlying adrenal hormone effects on memory consolidation and suggest that at least some degree of training-associated endogenous emotional arousal is essential for enabling their effects on memory consolidation. Our findings indicate that adrenal stress hormones influence memory consolidation of emotional experiences via interactions with arousal-induced activation of noradrenergic mechanisms within the amygdala.

Reviews in the Neurosciences, 2012

Acute stress and emotional arousal can enhance the consolidation of long-term memories in a manne... more Acute stress and emotional arousal can enhance the consolidation of long-term memories in a manner that is dependent on β-adrenoceptor activation in the basolateral complex of the amygdala (BLA). The BLA interacts with multiple memory systems in the brain to modulate a variety of classes of memory. However, the synaptic mechanisms of this interaction remain unresolved. This review describes the evidence of modulation of memory and synaptic plasticity produced by emotional arousal, stress hormones, and pharmacological or electrophysiological stimulation of the amygdala. The amygdala modulation of local translation and/or degradation of the synaptic plasticity-related proteins, activity-regulated cytoskeletal-associated protein and calcium/calmodulindependent protein kinase II α , is offered as a potential mechanism for the rapid memory consolidation that is associated with emotionally arousing events. This model shares features with synaptic tagging and the emotional tagging hypotheses.

Behavioural Pharmacology, 2003

Muscarinic cholinergic activation is a critical component of basolateral amygdala (BLA)-mediated ... more Muscarinic cholinergic activation is a critical component of basolateral amygdala (BLA)-mediated modulation of memory consolidation. The receptor(s) mediating this activation during consolidation have not been elucidated. This study investigated the roles of muscarinic subtype 1 (m1) and subtype 2 (m2) receptors in memory enhancement, by post-training intra-BLA infusions of the nonselective muscarinic agonist oxotremorine. Rats received intra-BLA infusions of either oxotremorine alone (10 lg in 0.2 ll per side), oxotremorine together with the selective m1 antagonist telenzipine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine with the selective m2 antagonist methoctramine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine with a combination of the above doses of telenzipine and methoctramine, or only vehicle, immediately after inhibitory avoidance training. Performance on a 48-hour retention test was significantly enhanced in oxotremorine-treated rats relative to vehicle-infused controls. Intra-BLA coinfusion of oxotremorine with either telenzipine (5, 17 or 50 nmol/side) or methoctramine (17 or 50 nmol/side) blocked the oxotremorine-induced enhancement. Combinations of these antagonists did not act additively to block memory enhancement by oxotremorine. These findings indicate that modulation of memory consolidation induced by cholinergic influences within the BLA requires activation of both m1 and m2 receptor synapses. Plausible mechanisms for m1-and m2-mediated influences on BLA circuitry are discussed.

Memory consolidation: Essays in honor of James L. McGaugh., 2001

Cognitive Behaviour Therapy, 2015

Brain-derived neurotrophic factor (BDNF) is associated with synaptic plasticity, which is crucial... more Brain-derived neurotrophic factor (BDNF) is associated with synaptic plasticity, which is crucial for long-term learning and memory. Some studies suggest that people suffering from anxiety disorders show reduced BDNF relative to healthy controls. Lower BDNF is associated with impaired learning, cognitive deficits, and poor exposure-based treatment outcomes. A series of studies with rats showed that exercise elevates BDNF and enhances fear extinction. However, this strategy has not been tested in humans. In this pilot study, we randomized participants (N = 9, 8 females, M Age = 34) with posttraumatic stress disorder (PTSD) to (a) prolonged exposure alone (PE) or (b) prolonged exposure + exercise (PE + E). Participants randomized to the PE + E condition completed a 30-minute bout of moderate-intensity treadmill exercise (70% of agepredicted HR max) prior to each PE session. Consistent with prediction, the PE + E group showed a greater improvement in PTSD symptoms (d = 2.65) and elevated BDNF (d = 1.08) relative to the PE only condition. This pilot study provides initial support for further investigation into exercise augmented exposure therapy.

Frontiers in Pharmacology, 2017

High levels of emotional arousal can impair spatial memory mediated by the hippocampus, and enhan... more High levels of emotional arousal can impair spatial memory mediated by the hippocampus, and enhance stimulus-response (S-R) habit memory mediated by the dorsolateral striatum (DLS). The present study was conducted to determine whether these memory systems may be similarly affected in an animal model of post-traumatic stress disorder (PTSD). Sprague-Dawley rats were subjected to a "single-prolonged stress" (SPS) procedure and 1 week later received training in one of two distinct versions of the plus-maze: a hippocampus-dependent place learning task or a DLS-dependent response learning task. Results indicated that, relative to non-stressed control rats, SPS rats displayed slower acquisition in the place learning task and faster acquisition in the response learning task. In addition, extinction of place learning and response learning was impaired in rats exposed to SPS, relative to non-stressed controls. The influence of SPS on hippocampal spatial memory and DLS habit memory observed in the present study may be relevant to understanding some common features of PTSD, including hippocampal memory deficits, habit-like avoidance responses to trauma-related stimuli, and greater likelihood of developing drug addiction and alcoholism.

Frontiers in Behavioral Neuroscience

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by experiencing or wi... more Posttraumatic stress disorder (PTSD) is a mental health condition triggered by experiencing or witnessing a terrifying event that can lead to lifelong burden that increases mortality and adverse health outcomes. Yet, no new treatments have reached the market in two decades. Thus, screening potential interventions for PTSD is of high priority. Animal models often serve as a critical translational tool to bring new therapeutics from bench to bedside. However, the lack of concordance of some human clinical trial outcomes with preclinical animal efficacy findings has led to a questioning of the methods of how animal studies are conducted and translational validity established. Thus, we conducted a systematic review to determine methodological variability in studies that applied a prominent animal model of trauma-like stress, single prolonged stress (SPS). The SPS model has been utilized to evaluate a myriad of PTSD-relevant outcomes including extinction retention. Rodents exposed to SPS...

Bioelectronics in Medicine