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Erschienen in: Brain Structure and Function 7/2021

10.07.2021 | Original Article

Chemogenetic inhibition of prefrontal projection neurons constrains top–down control of attention in young but not aged rats

verfasst von: Michael R. Duggan, Surbhi Joshi, Jacob Strupp, Vinay Parikh

Erschienen in: Brain Structure and Function | Ausgabe 7/2021

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Abstract

The prefrontal cortex (PFC) governs top–down control of attention and is known to be vulnerable in aging. Cortical reorganization with increased PFC recruitment is suggested to account for functional compensation. Here, we hypothesized that reduced PFC output would exert differential effects on attentional capacities in young and aged rats, with the latter exhibiting a more robust decline in performance. A chemogenetic approach involving designer receptors exclusively activated by designer drugs was utilized to determine the impact of silencing PFC projection neurons in rats performing an operant attention task. Visual distractors were presented in all behavioral testing sessions to tax attentional resources. Under control conditions, aged rats exhibited impairments in discriminating signals with the shortest duration from non-signal events. Surprisingly, chemogenetic inhibition of PFC output neurons did not worsen performance amongst aged animals. Conversely, significant impairments in attentional capacities were observed in young subjects following such manipulation. Given the involvement of PFC-projecting basal forebrain cholinergic neurons in top–down regulation of attention, amperometric recordings were conducted to measure alterations in prefrontal cholinergic transmission in a separate cohort of young and aged rats. While PFC silencing resulted in a robust attenuation of tonic cholinergic signaling across age groups, the capacity to generate phasic cholinergic transients was impaired only amongst young animals. Collectively, our findings suggest a reduced efficiency of PFC-mediated top–down control of attention and cholinergic system in aging, and that activity of PFC output neurons does not reflect compensation in aged rats, at least in the attention domain.
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Literatur
Zurück zum Zitat Cabeza R, Dennis NA (2012) Frontal lobes and aging. In: Knight DTSRT (ed) Principles of frontal lobe function, 2nd edn. Oxford University Press, New York, pp 628–652 Cabeza R, Dennis NA (2012) Frontal lobes and aging. In: Knight DTSRT (ed) Principles of frontal lobe function, 2nd edn. Oxford University Press, New York, pp 628–652
Zurück zum Zitat Zaborszky L, Duque A, Gielow M, Gombkoto P, Nadasdy Z, Somogyi J (2015) Organization of the basal forebrain cholinergic projection system: specific or diffuse? In: Paxinos G (ed) The rat nervous system, 4th edn. Academic Press, San Diego, pp 491–507 CrossRef Zaborszky L, Duque A, Gielow M, Gombkoto P, Nadasdy Z, Somogyi J (2015) Organization of the basal forebrain cholinergic projection system: specific or diffuse? In: Paxinos G (ed) The rat nervous system, 4th edn. Academic Press, San Diego, pp 491–507 CrossRef
Metadaten
Titel
Chemogenetic inhibition of prefrontal projection neurons constrains top–down control of attention in young but not aged rats
verfasst von
Michael R. Duggan
Surbhi Joshi
Jacob Strupp
Vinay Parikh
Publikationsdatum
10.07.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 7/2021
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-021-02336-2