Astrocytes in CA1 modulate schema establishment in the hippocampal-cortical neuron network

Abstract

Background Schema, a concept from cognitive psychology used to explain how new information is integrated with previous experience, is a framework of acquired knowledge within associative network structures as biological correlate, which allows new relevant information to be quickly assimilated by parallel cortical encoding in the hippocampus (HPC) and cortex. Previous work demonstrated that myelin generation in the anterior cingulate cortex (ACC) plays a critical role for dynamic paired association (PA) learning and consolidation, while astrocytes in ACC play a vital role in cognitive decision-making. However, circuit components and mechanism involving HPC-anterior cingulate cortex (ACC) during schema formation remain uncertain. Moreover, the correlation between HPC-ACC circuit and HPC astrocytic activity is unclear. Results Utilizing a paired association (PA) behavioral paradigm, we dynamically recorded calcium signals of CA1-ACC projection neurons and ACC neurons during schema formation. Depending on the characteristics of the calcium signals, three distinct stages of schema establishment process were identified. The recruitment of CA1-ACC network was investigated in each stage under CA1 astrocytes Gi pathway chemogenetic activation. Results showed that CA1-ACC projecting neurons excitation gradually decreased along with schema development, while ACC neurons revealed an excitation peak in the middle stage. CA1 astrocytic Gi pathway activation will disrupt memory schema development by reducing CA1-ACC projection neuron recruitment in the initial stage and prevent both CA1-ACC projection neurons and ACC neuron excitation in the middle stage. CA1 astrocytes Gi markedly suppress new PA assimilation into the established memory schema. Conclusions These results not only reveal the dynamic feature of CA1-ACC network during schema establishment, but also suggest CA1 astrocyte contribution in different stages of schema establishment.

Astrocytic L-lactate signaling in the anterior cingulate cortex is essential for schema memory and neuronal mitochondrial biogenesis

“…At S17 the mean PI reached the maximum level (77%). This result is consistent with the other reports (Tse et al, 2007; Hasan et al, 2019; Liu, S. et al, 2022). However, the hM4Di-CNO group consistently had lower mean PI (Fig.…”

“…Training rats with several PAs leads to schema formation which is stored in the ACC and the learnt PAs gradually become hippocampus independent (Tse et al, 2007; Tse et al, 2011; Hasan et al, 2019; Liu, S. et al, 2022). Astrocytic G i pathway activation was shown to modulate different cognitive functions (Jones et al, 2018; Kol et al, 2020; Liu, S. et al, 2022). However, the effect of ACC astrocytic G i activation on schema memory is yet unknown.…”

“…Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are genetically modified GPCRs which allow researchers to control cellular activity via modulation of GPCR signaling with the application of selective ligands (Urban & Roth, 2015; Yu et al, 2020). These chemogenetic tools have been used to modulate the function of neurons and astrocytes in different brain regions (Armbruster et al, 2007; Alexander et al, 2009; Zhu et al, 2014; Koike et al, 2016; Adamsky et al, 2018; Jones et al, 2018; Durkee et al, 2019; Pati et al, 2019; Kol et al, 2020; Oguchi et al, 2021; Lei et al, 2022; Liu, S. et al, 2022). Using chemogenetic approach, astrocytic G i pathway activation in hippocampus has recently been shown to modulate cognitive functions (Jones et al, 2018; Kol et al, 2020; Liu, S. et al, 2022), although the mechanism is still not fully understood.…”

“…These chemogenetic tools have been used to modulate the function of neurons and astrocytes in different brain regions (Armbruster et al, 2007; Alexander et al, 2009; Zhu et al, 2014; Koike et al, 2016; Adamsky et al, 2018; Jones et al, 2018; Durkee et al, 2019; Pati et al, 2019; Kol et al, 2020; Oguchi et al, 2021; Lei et al, 2022; Liu, S. et al, 2022). Using chemogenetic approach, astrocytic G i pathway activation in hippocampus has recently been shown to modulate cognitive functions (Jones et al, 2018; Kol et al, 2020; Liu, S. et al, 2022), although the mechanism is still not fully understood. Moreover, how astrocytic G i signaling in the anterior cingulate cortex (ACC) affects cognitive functions – particularly schema memory - is yet unknown.…”

Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats

“…Astrocytes are able to differentiate the activity of discrete synapses that originate from different afferents and modify synaptic activity at surrounding synapses by releasing active substances 22 to modulate various neuronal circuits 30,36,[69][70][71] , and affect behavioural responses 29,38,72,73 . It has been well demonstrated that astrocytes support neuronal functions by regulating the flow of extracellular ions and neurotransmitters, and by providing neuronal energy substrates such as lactate by means of their astrocytic processes.…”