Multiscale Imaging Reveals Aberrant Functional Connectome Organization and Elevated Dorsal Striatal<i>Arc</i>Expression in Advanced Age

Colon-Perez, Luis M.; Turner, Sean M.; Lubke, Katelyn N.; Pompilus, Marjory; Febo, Marcelo; Burke, Sara N.

doi:10.1523/eneuro.0047-19.2019

Cited by 16 publications

(32 citation statements)

References 100 publications

(145 reference statements)

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“…It is well established that the frequency bandwidth of spontaneous BOLD signal oscillations falls within previously characterized infraslow frequencies (<0.5) that cover a large expanse of rat cortex (60,61). Studies in primate visual cortex have also shown that normalized spectral frequencies in the band limited power for gamma (40-100Hz) share a high degree of statistical dependency (mutual information) with the fMRI BOLD signal while alpha (8)(9)(10)(11)(12) Hz), beta (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and higher frequency (0.9-3kHz) multi-unit activity much less so (62).…”

Section: Discussionmentioning

confidence: 81%

“…The paradigm used here did not generate a memory 'response' by the rats prior or after scanning and this weakens the direct linkage between the network differences between groups and their role in memory structure in the brain. Regarding the experimental paradigm itself, we have previously applied better validated and more system selective experimental paradigms for assessing learning and memory that allowed a priori hypothesis testing of the brain regions involved in memory processing (20,21). We anticipate future studies using similar paradigms here but with the added modification that the memory-retrieving process or the memory-signaling behavior be carried out or measured during a short temporal delay prior to imaging.…”

Section: Discussionmentioning

confidence: 99%

“…Performance on the MWM in aged male rats correlates with strength of default mode connectivity with the retrosplenial cortex (18), and weakening of CA1-prefrontal connectivity is associated age-related decline in learning (19). An index of rich club organization, which reflects the presence of a small group of very high degree 'hub' nodes, was observed to be greater in aged versus young male rats, and increased as a function of cognitive training (20). Longitudinal decline in memory was linked to changes in functional connectivity between the dorsal hippocampus and retrosplenial cortex, thalamus, striatum, and amygdala (21).…”

Section: Introductionmentioning

confidence: 88%

“…A fat saturation pulse was used to suppress chemical shift artifact and phase correction parameters were acquired during receiver gain adjustment for Nyquist ghost correction. Respiratory rates, isoflurane concentration, body temperature, lighting, and room conditions were kept constant across subjects (20).…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

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Contextual experience modifies functional connectome indices of topological strength and organization

Pompilus

Colon-Perez

Grudny

et al. 2020

Preprint

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Stimuli presented at short temporal delays before functional magnetic resonance imaging (fMRI) can have a robust impact on the organization of synchronous activity in resting state networks. This presents an opportunity to investigate how sensory, affective and cognitive stimuli alter functional connectivity in rodent models. Here, we assessed the effect of a familiar contextual stimulus presented 10 minutes prior to sedation for imaging on functional connectivity. A subset of animals were co-presented with an unfamiliar social stimulus in the same environment to further investigate the effect of familiarity on network topology. Female and male rats were imaged at 11.1 Tesla and graph theory analysis was applied to matrices generated from seed-based functional connectivity data sets with 144 nodes and 10,296 edge weights. Our results show an unconventional network topology in response to the familiar (context) but not the unfamiliar (social) stimulus. The familiar stimulus strongly reduced network strength, global efficiency, and altered the location of the highest eigenvector centrality nodes from cortex to the hypothalamus. We did not observe changes in modular organization, nodal cartographic assignments, assortative mixing, rich club organization, and network resilience.The results suggest that experiential factors, perhaps involving associative or episodic memory, can exert a dramatic effect on functional network strength and efficiency when presented at a short temporal delay before imaging.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

See 2 more Smart Citations

Contextual experience modifies functional connectome indices of topological strength and organization

Pompilus

Colon-Perez

Grudny

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Performance on the MWM in aged male rats correlates with strength of default mode connectivity with the retrosplenial cortex 16 , and weakening of CA1-prefrontal connectivity is associated age-related decline in learning 17 . An index of rich club organization, which reflects the presence of a small group of very high degree ‘hub’ nodes, was observed to be greater in aged versus young male rats, and increased as a function of cognitive training 18 . Longitudinal decline in memory was linked to changes in functional connectivity between the dorsal hippocampus and retrosplenial cortex, thalamus, striatum, and amygdala 19 .…”

Section: Introductionmentioning

confidence: 94%

Contextual experience modifies functional connectome indices of topological strength and efficiency

Pompilus

Colon-Perez

Grudny

et al. 2020

Sci Rep

Self Cite

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Stimuli presented at short temporal delays before functional magnetic resonance imaging (fMRI) can have a robust impact on the organization of synchronous activity in resting state networks. This presents an opportunity to investigate how sensory, affective and cognitive stimuli alter functional connectivity in rodent models. In the present study we assessed the effect on functional connectivity of a familiar contextual stimulus presented 10 min prior to sedation for imaging. A subset of animals were co-presented with an unfamiliar social stimulus in the same environment to further investigate the effect of familiarity on network topology. Rats were imaged at 11.1 T and graph theory analysis was applied to matrices generated from seed-based functional connectivity data sets with 144 brain regions (nodes) and 10,152 pairwise correlations (after excluding 144 diagonal edges). Our results show substantial changes in network topology in response to the familiar (context). Presentation of the familiar context, both in the absence and presence of the social stimulus, strongly reduced network strength, global efficiency, and altered the location of the highest eigenvector centrality nodes from cortex to the hypothalamus. We did not observe changes in modular organization, nodal cartographic assignments, assortative mixing, rich club organization, and network resilience. We propose that experiential factors, perhaps involving associative or episodic memory, can exert a dramatic effect on functional network strength and efficiency when presented at a short temporal delay before imaging.

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Rodent mnemonic similarity task performance requires the prefrontal cortex

et al. 2021

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Mnemonic similarity task performance, in which a known target stimulus must be distinguished from similar lures, is supported by the hippocampus and perirhinal cortex.Impairments on this task are known to manifest with advancing age. Interestingly, disrupting hippocampal activity leads to mnemonic discrimination impairments when lures are novel, but not when they are familiar. This observation suggests that other brain structures support discrimination abilities as stimuli are learned. The prefrontal cortex (PFC) is critical for retrieval of remote events and executive functions, such as working memory, and is also particularly vulnerable to dysfunction in aging. Importantly, the medial PFC is reciprocally connected to the perirhinal cortex and neuron firing in this region coordinates communication between lateral entorhinal and perirhinal cortices to presumably modulate hippocampal activity. This anatomical organization and function of the medial PFC suggests that it contributes to mnemonic discrimination; however, this notion has not been empirically tested. In the current study, rats were trained on a LEGO object-based mnemonic similarity task adapted for rodents, and surgically implanted with guide cannulae targeting prelimbic and infralimbic regions of the medial PFC. Prior to mnemonic discrimination tests, rats received PFC infusions of the GABA A agonist muscimol. Analyses of expression of the neuronal activity-dependent immediate-early gene Arc in medial PFC and adjacent cortical regions confirmed muscimol infusions led to neuronal inactivation in the infralimbic and prelimbic cortices. Moreover, muscimol infusions in PFC impaired mnemonic discrimination performance relative to the vehicle control across all testing blocks when lures shared 50-90% feature overlap with the target. Thus, in contrast hippocampal infusions, PFC inactivation impaired target-lure discrimination regardless of the novelty or familiarity of the lures. These findings indicate the PFC plays a critical role in mnemonic similarity task performance, but the time course of PFC involvement is dissociable from that of the hippocampus.

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Multiscale Imaging Reveals Aberrant Functional Connectome Organization and Elevated Dorsal StriatalArcExpression in Advanced Age

Cited by 16 publications

References 100 publications

Contextual experience modifies functional connectome indices of topological strength and organization

Contextual experience modifies functional connectome indices of topological strength and organization

Contextual experience modifies functional connectome indices of topological strength and efficiency

Rodent mnemonic similarity task performance requires the prefrontal cortex

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