McIntyre-Rodriguez, Christa
Permanent URI for this collectionhttps://hdl.handle.net/10735.1/2875
Dr. McIntyre-Rodriguez's research is aimed at gaining information regarding the neuronal signals that determine whether a memory will be stored for the long term and may shed some light on the precise mechanisms involved in the synaptic changes that underlie memory. Such knowledge may ultimately be used to benefit individuals suffering from various memory disorders including Alzheimer's disease and post traumatic stress disorder.
Learn more about Christa McIntyre-Rodriguez on her BBS People and Research Explorer pages.Browse
Browsing McIntyre-Rodriguez, Christa by Subject "Anxiety"
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Item Impaired Spatial Memory and Enhanced Habit Memory in a Rat Model of Post-Traumatic Stress Disorder(Frontiers Media SA) Goodman, Jarid; McIntyre, Christa K.; Goodman, Jarid; McIntyre, Christa K.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.Item Vagus Nerve Stimulation as a Tool for Enhancing Extinction in Exposure-Based Therapies(Springer, 2019-01) Noble, Lindsey J.; Souza, Rimenez R.; McIntyre, Christa K.; 0000-0002-8138-5023 (McIntyre, CK); Noble, Lindsey J.; Souza, Rimenez R.; McIntyre, Christa K.Rationale Emotionally traumatic experiences can lead to maladaptive memories that are enduring and intrusive. The goal of exposure-based therapies is to extinguish conditioned fears through repeated, unreinforced exposures to reminders of traumatic events. The extinction of conditioned fear depends upon the consolidation of new memories made during exposure to reminders. An impairment in extinction recall, observed in certain patient populations, can interfere with progress in exposure-based therapies, and the drive to avoid thoughts and reminders of the trauma can undermine compliance and increase dropout rate. Effective adjuncts to exposure-based therapies should improve the consolidation and maintenance of the extinction memory or improve the tolerability of the therapy. Under stressful conditions, the vagus nerve responds to elevations in epinephrine and signals the brain to facilitate the storage of new memories while, as part of the parasympathetic nervous system, it slows the sympathetic response. Objective Here, we review studies relevant to fear extinction, describing the anatomical and functional characteristics of the vagus nerve and mechanisms of vagus nerve stimulation (VNS)-induced memory enhancement and plasticity. Results We propose that stimulation of the left cervical vagus nerve during exposure to conditioned cues signals the brain to store new memories just as epinephrine or emotional arousal would do, but bypasses the peripheral sympathetic fight-or-flight response. Conclusions In support of this hypothesis, we have found that VNS accelerates extinction and prevents reinstatement of conditioned fear in rats. Finally, we propose future studies targeting the optimization of stimulation parameters and the search for biomarkers of VNS effectiveness that may improve exposure therapy outcomes.Item Vagus Nerve Stimulation Promotes Generalization of Conditioned Fear Extinction and Reduces Anxiety in Rats(Elsevier Science Inc, 2018-09-21) Noble, Lindsey J.; Meruva, Venkat B.; Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.; McIntyre, Christa K.; 0000-0003-4225-241X (Hays, SA); 13146094343400332984 (Hays, SA); Noble, Lindsey J.; Meruva, Venkat B.; Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.; McIntyre, Christa K.Background: Exposure-based therapies are used to treat a variety of trauma- and anxiety-related disorders by generating successful extinction following cue exposure during treatment. The development of adjuvant strategies that accelerate extinction learning, improve tolerability, and increase efficiency of treatment could increase the efficacy of exposure-based therapies. Vagus nerve stimulation (VNS) paired with exposure can enhance fear extinction, in rat models of psychiatric disorders, and chronic administration of VNS reduces anxiety in rats and humans. Objective: We tested whether VNS, like other cognitive enhancers, could produce generalization of extinction for stimuli that are not presented during the extinction sessions, but are associated with the fear event. Methods: Male Sprague Dawley rats underwent auditory fear conditioning with two easily discriminable auditory stimuli. Following fear conditioning, extinction training consisted of exposure to only one of the conditioned sounds. Half of the rats received VNS and half received sham stimulation during with sound presentations. VNS effects on anxiety were examined in a separate study where VNS was administered prior to testing on the elevated plus maze. Results: Sham stimulated rats given 20 presentations of a conditioned stimulus (CS) during the extinction session showed performance that was matched to VNS-treated rats given only 4 presentations of the CS. Despite comparable levels of freezing to the presented CS, only the VNS-treated rats showed a significant decrease in freezing to the CS that was not presented. VNS-induced generalization of extinction was observed only when the two sounds were paired with footshock within the same fear conditioning session; VNS did not promote generalization of extinction when the two sounds were conditioned on different days or in different contexts. On the anxiety test, VNS administration significantly increased time spent in the open arms of the elevated plus maze. Conclusion: These results provide evidence that VNS can promote generalization of extinction to other stimuli associated with a specific fear experience. Furthermore, non-contingent VNS appears to reduce anxiety. The ability to generalize extinction and reduce anxiety makes VNS a potential candidate for use as an adjunctive strategy to improve the efficacy and tolerability of exposure-based therapies.Item Vagus Nerve Stimulation Reverses the Extinction Impairments in a Model of PTSD with Prolonged and Repeated Trauma(Taylor and Francis Ltd, 2019-04-23) Souza, Rimenez R.; Robertson, Nicole M.; Pruitt, David T.; Gonzales, Phillip A.; Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.; McIntyre, Crista K.; 0000-0003-4225-241X (Hays, SA); 13146094343400332984 (Hays, SA); Souza, Rimenez R.; Robertson, Nicole M.; Pruitt, David T.; Gonzales, Phillip A.; Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.; McIntyre, Crista K.We have shown that vagus nerve stimulation (VNS) enhances extinction of conditioned fear and reduces anxiety in rat models of PTSD using moderate stress. However, it is still unclear if VNS can be effective in enhancing extinction of severe fear after prolonged and repeated trauma. Severe fear was induced in adult male rats by combining single prolonged stress (SPS) and protracted aversive conditioning (PAC). After SPS and PAC procedures, rats were implanted with stimulating cuff electrodes, exposed to five days of extinction training with or without VNS, and then tested for extinction retention, return of fear in a new context and reinstatement. The elevated plus maze, open field and startle were used to test anxiety. Sham rats showed no reduction of fear during extensive extinction training. VNS-paired with extinction training reduced freezing at the last extinction session by 70% compared to sham rats. VNS rats exhibited half as much fear as shams, as well as less fear renewal. Sham rats exhibited significantly more anxiety than naive controls, whereas VNS rats did not. These results demonstrate that VNS enhances extinction and reduces anxiety in a severe model of PTSD that combined SPS and a conditioning procedure that is 30 times more intense than the conditioning procedures in previous VNS studies. The broad utility of VNS in enhancing extinction learning in rats and the strong clinical safety record of VNS suggest that VNS holds promise as an adjuvant to exposure-based therapy in people with PTSD and other complex forms of this condition. ©2019 Informa UK Limited, trading as Taylor & Francis Group.