Abstract
Higher cognitive processes and emotional regulation depend on densely interconnected telencephalic and limbic areas. Central structures of this cortico-limbic network are ventral hippocampus (vHC), medial prefrontal cortex (PFC), basolateral amygdala (BLA) and nucleus accumbens (NAC). Human and animal studies have revealed both anatomical and functional alterations in specific connections of this network in several psychiatric disorders. However, it is often not clear whether functional alterations within these densely interconnected brain areas are caused by modifications in the direct pathways, or alternatively through indirect interactions. We performed multi-site extracellular recordings of spontaneous activity in three different brain regions to study the functional connectivity in the BLA–NAC–PFC–vHC network of the lightly anesthetized mouse in vivo. We show that BLA, NAC, PFC and vHC are functionally connected in distinct frequency bands and determined the influence of a third brain region on this connectivity. In addition to describing mutual synchronicity, we determined the strength of functional connectivity for each region in the BLA–NAC–PFC–vHC network. We find a region-specificity in the strength of feedforward and feedback connections for each region in its interaction with other areas in the network. Our results provide insights into functional and directed connectivity in the cortico-limbic network of adult wild-type mice, which may be helpful to further elucidate the pathophysiological changes of this network in psychiatric disorders and to develop target-specific therapeutic interventions.
Highlights
Higher cognitive processes and emotional regulation, such as associative learning, episodic memory formation, decision making, threat processing, and anxiety, depend
We demonstrate that ventral hippocampus (vHC)–basolateral amygdala (BLA)–nucleus accumbens (NAC)–prefrontal cortex (PFC) are highly interconnected in their LFP and spike activity
The strongest power of LFP in BLA, NAC and PFC were observed in the delta band and in vHC in both delta and theta bands
Summary
All procedures related to the care and treatments of animals were approved by a local ethics committee (#23 17707/G 14-1-080) and followed the German and European national regulations (European Communities Council Directive, 86/609/EEC). Anesthesia was induced by 5% isoflurane and maintained during surgery by a combination of urethane (375 mg/kg, ip), chlorprothixene hydrochloride (2 mg/kg, ip) and isoflurane (1–2%). Isoflurane was reduced to 0% to minimize anesthesia-induced unwanted side effects on neural activity and functional connectivity (Williams et al 2010; Bukhari et al 2018; Paasonen et al 2018). Functional connectivity of the default mode network, interhemispheric and complex-network parameters (e.g. correlation coefficients, modularity, clustering coefficients) and thalamocortical connectivity is better preserved in urethane anesthesia as compared to the other anesthetics tested (Paasonen et al 2018). Depending on the level of anesthesia as assessed by the breathing rate and presence or absence of the pinch toe reflex, additional doses of chlorprothixene hydrochloride (2 mg/kg, ip) were injected (after approximately 3 h).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
