Effects of spreading depolarization induced by amygdala micro-injury on fear memory in rats
- Авторлар: Smirnova M.P.1, Pavlova I.V.1, Vinogradova L.V.1
-
Мекемелер:
- Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences
- Шығарылым: Том 18, № 4 (2023)
- Беттер: 727-730
- Бөлім: Conference proceedings
- ##submission.dateSubmitted##: 13.11.2023
- ##submission.dateAccepted##: 20.11.2023
- ##submission.datePublished##: 15.12.2023
- URL: https://genescells.ru/2313-1829/article/view/623274
- DOI: https://doi.org/10.17816/gc623274
- ID: 623274
Дәйексөз келтіру
Ашық рұқсат
Рұқсат берілді
Рұқсат ақылы немесе тек жазылушылар үшін
Аннотация
Spreading depolarization (SD) is a wave of intense neuroglial depolarization that is widely recognized as a component of the acute brain response to various types of injury. Clinical studies conducted on patients with different types of stroke and traumatic brain injury which used intracranial recordings of cortical activity revealed a frequent incidence of cortical SD [1]. Site-specific intracerebral microinjections of drugs in experimental animals, or functional stereotactic surgery in patients, cause damage to both the neocortex and subcortical structures in the local area. Currently, most studies on SD are limited to the neocortex, but research shows that SD can be triggered in nearly all brain structures, albeit with varying levels of effectiveness [2]. The underlying mechanisms that render deep brain structures more vulnerable to SD remain unclear. Our recent research found that local injury to the amygdala can also lead to SD, although with a reduced likelihood compared to the neocortex [3]. The amygdala, a structure located in the temporal lobe, is highly susceptible to brain injury and plays a significant role in emotional behavior [4]. Specifically, it serves as a pivotal hub for fear memory and post-traumatic stress disorder pathogenesis. The post-injury neurobehavioral impairments are attributed to the limbic structure. Patients suffering from traumatic brain injury and stroke often exhibit cognitive dysfunction, generalized anxiety disorder, posttraumatic stress disorder, and other neuropsychiatric states. The role of SD in the pathogenesis of the behavioral deficit and its underlying mechanisms are not well understood.
In this study, we examined the impact of amygdala micro-injury and associated SD on fear memory in rats. Neuronal tissue damage was induced using the standard method of intracerebral injection of substances through a thin 30 G needle inserted into a guide cannula (23 G) previously implanted in the amygdala. We used the classical Pavlovian fear conditioning paradigm to assess animal behavior. Twenty-four hours following the acquisition of fear, fear memory was evaluated during the first test. An hour after the first test, bilateral microinjury of the amygdala was performed. The influence of amygdala microinjury on aversive memory was assessed during the second test 24 hours later. Following the second test, rats underwent a two-day fear extinction process one to two days later.
We found that bilateral micro-injury to the amygdala resulted in bilateral SD, unilateral SD, or no SD. Neither the injury nor the SD induced significant changes in fear conditioning during test 2, but they did affect subsequent fear extinction. The effect depended on whether the SD was triggered by the injury. If no SD occurred, fear extinction was disrupted, and rats exhibited high levels of freezing in response to sound. However, if bilateral SD was triggered by amygdala damage, fear memory was extinguished successfully and rapidly. The results of the present study suggest a strong involvement of SD induced by amygdala micro-injury in fear memory extinction.
This information is crucial in comprehending the fundamental mechanisms behind post-traumatic stress disorder and exploring novel therapeutic approaches for treating this condition. The discoveries could be valuable in designing and interpreting experiments that involve local intracerebral microinjection.
Негізгі сөздер
Толық мәтін
Spreading depolarization (SD) is a wave of intense neuroglial depolarization that is widely recognized as a component of the acute brain response to various types of injury. Clinical studies conducted on patients with different types of stroke and traumatic brain injury which used intracranial recordings of cortical activity revealed a frequent incidence of cortical SD [1]. Site-specific intracerebral microinjections of drugs in experimental animals, or functional stereotactic surgery in patients, cause damage to both the neocortex and subcortical structures in the local area. Currently, most studies on SD are limited to the neocortex, but research shows that SD can be triggered in nearly all brain structures, albeit with varying levels of effectiveness [2]. The underlying mechanisms that render deep brain structures more vulnerable to SD remain unclear. Our recent research found that local injury to the amygdala can also lead to SD, although with a reduced likelihood compared to the neocortex [3]. The amygdala, a structure located in the temporal lobe, is highly susceptible to brain injury and plays a significant role in emotional behavior [4]. Specifically, it serves as a pivotal hub for fear memory and post-traumatic stress disorder pathogenesis. The post-injury neurobehavioral impairments are attributed to the limbic structure. Patients suffering from traumatic brain injury and stroke often exhibit cognitive dysfunction, generalized anxiety disorder, posttraumatic stress disorder, and other neuropsychiatric states. The role of SD in the pathogenesis of the behavioral deficit and its underlying mechanisms are not well understood.
In this study, we examined the impact of amygdala micro-injury and associated SD on fear memory in rats. Neuronal tissue damage was induced using the standard method of intracerebral injection of substances through a thin 30 G needle inserted into a guide cannula (23 G) previously implanted in the amygdala. We used the classical Pavlovian fear conditioning paradigm to assess animal behavior. Twenty-four hours following the acquisition of fear, fear memory was evaluated during the first test. An hour after the first test, bilateral microinjury of the amygdala was performed. The influence of amygdala microinjury on aversive memory was assessed during the second test 24 hours later. Following the second test, rats underwent a two-day fear extinction process one to two days later.
We found that bilateral micro-injury to the amygdala resulted in bilateral SD, unilateral SD, or no SD. Neither the injury nor the SD induced significant changes in fear conditioning during test 2, but they did affect subsequent fear extinction. The effect depended on whether the SD was triggered by the injury. If no SD occurred, fear extinction was disrupted, and rats exhibited high levels of freezing in response to sound. However, if bilateral SD was triggered by amygdala damage, fear memory was extinguished successfully and rapidly. The results of the present study suggest a strong involvement of SD induced by amygdala micro-injury in fear memory extinction.
This information is crucial in comprehending the fundamental mechanisms behind post-traumatic stress disorder and exploring novel therapeutic approaches for treating this condition. The discoveries could be valuable in designing and interpreting experiments that involve local intracerebral microinjection.
ADDITIONAL INFORMATION
Funding sources. This work was supported by Russian Science Foundation (grant No. 22-15-00327).
Авторлар туралы
M. Smirnova
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences
Хат алмасуға жауапты Автор.
Email: rymarik@gmail.com
Ресей, Moscow
I. Pavlova
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences
Email: rymarik@gmail.com
Ресей, Moscow
L. Vinogradova
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences
Email: rymarik@gmail.com
Ресей, Moscow
Әдебиет тізімі
- Lauritzen M, Strong AJ. ‘Spreading depression of Leão’ and its emerging relevance to acute brain injury in humans. Journal of Cerebral Blood Flow & Metabolism. 2017;37(5):1553–1570. doi: 10.1177/0271678X16657092
- Andrew RD, Hartings JA, Ayata C, et al. The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention. Neurocritical Care. 2022;37(Suppl 1):83–101. doi: 10.1007/s12028-021-01431-w
- Vinogradova LV, Rysakova MP, Pavlova IV. Small damage of brain parenchyma reliably triggers spreading depolarization. Neurological Research. 2020;42(1):76–82. doi: 10.1080/01616412.2019.1709745
- Gafford G, Ressler K. Mouse models of fear-related disorders: Cell-type-specific manipulations in amygdala. Neuroscience. 2016;321:108–120. doi: 10.1016/j.neuroscience.2015.06.019
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