Functional and directed connectivity of the cortico-limbic network in mice in vivo

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.

Altered Structural and Functional Abnormalities of Hippocampus in Classical Trigeminal Neuralgia: A Combination of DTI and fMRI Study

“…Now, there is a consensus that pain could cause not only sensory dysfunction but also miscellaneous functional brain shambles when it becomes persistent or chronic, such as anxiety, retrograde amnesia, agrypnia, and depression [ 32 , 33 ]. Hippocampus is an integral component of the limbic system [ 34 ], which has been connected with some functions such as learning and memory [ 35 ], emotion and affect [ 36 ], and sensory-motor integration [ 37 ]. Intriguingly, a cortical-limbic pathway has been depicted to transit from S1 and S2 to the IC and parietal cortical structures, then to the amygdala, the perirhinal cortex, and the hippocampus.…”

Commentary: Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors

“…The experimental procedure of this study is impressive, but we still wish to discuss some details. First, NAc could not only receive neural projections from BLA, but it could also induce changes in anxiety behavior in previous studies (Zhang et al, 2020;Huang et al, 2021;Khastkhodaei et al, 2021). Sun et al discovered that the VTA-BLA-NAc neural circuit regulates reward effects and motivated behavior (Sun et al, 2021).…”

Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors

“…The corticolimbic system, which consists of the prefrontal cortices, the hippocampus, and the amygdala, processes higher cognitive functions, including memory formation, decision-making, and emotional regulation [48,49]. Dysfunction of GABAergic interneurons, which mediate regulation and coordination of cortical pyramidal neuron activity [50], may be involved in epilepsy [51], schizophrenia, and anxiety [52].…”