TY - JOUR
T1 - Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice
AU - Grohs-Metz, Gillian
AU - Smausz, Rebecca
AU - Gigg, John
AU - Boeckers, Tobias
AU - Hengerer, Bastian
N1 - Funding Information:
This work was funded by Boehringer Ingelheim Pharma GmbH & Co. Funding comprised of PhD stipend/salaries of the authors GGM & BH, consumables, animals, equipment, open access and color print charges (CNS Diseases Research). Behavioral tests, imaging experiments and computational analysis were conducted in the laboratories of Boehringer Ingelheim Pharma GmbH & Co. The funder did not have any additional role in study design, data collection and analysis, decision to publish or preparation of the article. There are no patents, products in development, or marketed products to declare. RS was funded by ERASMUS and Boehringer Ingelheim Pharma GmbH & Co. as part of an industrial placement from the University of Manchester Faculty of Biology, Medicine and Health
Publisher Copyright:
© 2022 The Authors
PY - 2022/6/25
Y1 - 2022/6/25
N2 - Emotional learning and memory are affected in numerous psychiatric disorders. At a systems level, however, the underlying neural circuitry is not well defined. Rodent fear conditioning (FC) provides a translational model to study the networks underlying associative memory retrieval. In the current study, functional connectivity among regions related to the cue associative fear network were investigated using functional ultrasound (fUS), a novel imaging technique with great potential for detecting neural activity through cerebral blood flow. Behavioral fear expression and fUS imaging were performed one and thirty-one days after FC to assess recent and remote memory recall. Cue-evoked increases in functional connectivity were detected throughout the amygdala, with the lateral (LA) and central (CeA) amygdalar nuclei emerging as major hubs of connectivity, although CeA connectivity was reduced during remote recall. Hippocampal and sensory cortical regions displayed heightened connectivity with the LA during remote recall, whereas interconnectivity between the primary auditory cortex and temporal association areas was reduced. Subregions of the prefrontal cortex exhibited variable changes, where prelimbic connectivity with the amygdala was refined while specific connections between the infralimbic cortex and amygdalar subregions emerged during remote memory retrieval, a signature of extinction memory. Moreover, freezing behavior positively correlated with functional connectivity between hubs of the associative fear network, suggesting that emotional response intensity reflected the strength of the cue-evoked functional network. Overall, our data provide evidence of the functionality of fUS imaging to investigate the neural dynamics of memory retrieval, applicable in the development of innovative treatments for affective disorders.
AB - Emotional learning and memory are affected in numerous psychiatric disorders. At a systems level, however, the underlying neural circuitry is not well defined. Rodent fear conditioning (FC) provides a translational model to study the networks underlying associative memory retrieval. In the current study, functional connectivity among regions related to the cue associative fear network were investigated using functional ultrasound (fUS), a novel imaging technique with great potential for detecting neural activity through cerebral blood flow. Behavioral fear expression and fUS imaging were performed one and thirty-one days after FC to assess recent and remote memory recall. Cue-evoked increases in functional connectivity were detected throughout the amygdala, with the lateral (LA) and central (CeA) amygdalar nuclei emerging as major hubs of connectivity, although CeA connectivity was reduced during remote recall. Hippocampal and sensory cortical regions displayed heightened connectivity with the LA during remote recall, whereas interconnectivity between the primary auditory cortex and temporal association areas was reduced. Subregions of the prefrontal cortex exhibited variable changes, where prelimbic connectivity with the amygdala was refined while specific connections between the infralimbic cortex and amygdalar subregions emerged during remote memory retrieval, a signature of extinction memory. Moreover, freezing behavior positively correlated with functional connectivity between hubs of the associative fear network, suggesting that emotional response intensity reflected the strength of the cue-evoked functional network. Overall, our data provide evidence of the functionality of fUS imaging to investigate the neural dynamics of memory retrieval, applicable in the development of innovative treatments for affective disorders.
KW - Associative memory retrieval
KW - Auditory cued fear conditioning
KW - Functional ultrasound imaging
KW - Neural networks
KW - Recent and remote emotional memory
U2 - 10.1016/j.bbr.2022.113862
DO - 10.1016/j.bbr.2022.113862
M3 - Article
SN - 0166-4328
VL - 428
JO - Behav Brain Res
JF - Behav Brain Res
M1 - 113862
ER -