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 Author "Kilgard, Michael P."
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Item Effects of Vagus Nerve Stimulation on Extinction of Conditioned Fear and Post-Traumatic Stress Disorder Symptoms in RatsNoble, Lindsey J.; Gonzalez, I. J.; Meruva, V. B.; Callahan, Kathleen A.; Belfort, Benjamin D.; Ramanathan, K. R.; Meyers, Eric; Kilgard, Michael P.; Rennaker, Robert L.; McIntyre, Christa K.; Noble, Lindsey J.; Gonzalez, I. J.; Meruva, V. B.; Callahan, Kathleen A.; Belfort, Benjamin D.; Ramanathan, K. R.; Meyers, Eric; Kilgard, Michael P.; Rennaker, Robert L.; McIntyre, Christa K.Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.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.