Neural correlates of the motherâ toâ infant social transmission of fear

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/119096/1/jnr23739.pd

Directly reactivated, but not indirectly reactivated, memories undergo reconsolidation in the amygdala.

International audienceMemory consolidation refers to a process by which newly learned information is made resistant to disruption. Traditionally, consolidation has been viewed as an event that occurs once in the life of a memory. However, considerable evidence now indicates that consolidated memories, when reactivated through retrieval, become labile (susceptible to disruption) again and undergo reconsolidation. Because memories are often interrelated in complex associative networks rather than stored in isolation, a key question is whether reactivation of one memory makes associated memories labile in a way that requires reconsolidation. We tested this in rats by creating interlinked associative memories using a second-order fear-conditioning task. We found that directly reactivated memories become labile, but indirectly reactivated (i.e., associated) memories do not. This suggests that memory reactivation produces content-limited rather than wholesale changes in a memory and its associations and explains why each time a memory is retrieved and updated, the entire associative structure of the memory is not grossly altered

Auditory fear conditioning and long-term potentiation in the lateral amygdala require ERK/MAP kinase signaling in the auditory thalamus: a role for presynaptic plasticity in the fear system.

International audienceIn the present study, we examined the role of the auditory thalamus [medial division of the medial geniculate nucleus and the adjacent posterior intralaminar nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological manipulation of intracellular signaling pathways. In the first experiment, rats were given intrathalamic infusions of the MEK (mitogen-activated protein kinase-kinase) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene (U0126) before fear conditioning. Findings revealed that long-term memory (assessed at 24 h) was impaired, whereas short-term memory (assessed at 1-3 h) of fear conditioning was intact. In the second experiment, rats received immediate posttraining intrathalamic infusion of U0126, the mRNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), or infusion of the protein synthesis inhibitor anisomycin. Posttraining infusion of either U0126 or DRB significantly impaired long-term retention of fear conditioning, whereas infusion of anisomycin had no effect. In the final experiment, rats received intrathalamic infusion of U0126 before long-term potentiation (LTP)-inducing stimulation of thalamic inputs to the lateral nucleus of the amygdala (LA). Findings revealed that thalamic infusion of U0126 impaired LTP in the LA. Together, these results suggest the possibility that MGm/PIN cells that project to the LA contribute to memory formation via ERK (extracellular signal-regulated kinase)-mediated transcription, but that they do so by promoting protein synthesis-dependent plasticity locally in the LA

Acid-sensing ion channel 1a regulates the specificity of reconsolidation of conditioned threat responses

Recent research on altering threat memory has focused on a reconsolidation window. During reconsolidation, threat memories are retrieved and become labile. Reconsolidation of distinct threat memories is synapse dependent, whereas the underlying regulatory mechanism of the specificity of reconsolidation is poorly understood. We designed a unique behavioral paradigm in which a distinct threat memory can be retrieved through the associated conditioned stimulus. In addition, we proposed a regulatory mechanism by which the activation of acid-sensing ion channels (ASICs) strengthens the distinct memory trace associated with the memory reconsolidation to determine its specificity. The activation of ASICs by CO2 inhalation, when paired with memory retrieval, triggers the reactivation of the distinct memory trace, resulting in greater memory lability. ASICs potentiate the memory trace by altering the amygdala-dependent synaptic transmission and plasticity at selectively targeted synapses. Our results suggest that inhaling CO2 during the retrieval event increases the lability of a threat memory through a synapse-specific reconsolidation process

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry

BACKGROUND AND OBJECTIVES: COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19. METHODS: Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS: Of a total of 15128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19. 5848 (38.7%) patients received IVT-only, and 9280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted odds ratio [OR] 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour (OR 2.47; 95% CI 1.58-3.86) and 3-month mortality (OR 1.88; 95% CI 1.52-2.33).COVID-19 patients also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION: Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients. Current available data does not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in COVID-19 patients, or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring and establishing prognosis

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

BACKGROUND AND OBJECTIVES COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19. METHODS Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS Of a total of 15128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19. 5848 (38.7%) patients received IVT-only, and 9280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted odds ratio [OR] 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour (OR 2.47; 95% CI 1.58-3.86) and 3-month mortality (OR 1.88; 95% CI 1.52-2.33).COVID-19 patients also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients. Current available data does not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in COVID-19 patients, or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring and establishing prognosis