Fear learning induces α7-nicotinic acetylcholine receptor-mediated astrocytic responsiveness that is required for memory persistence

Förster, Rita; He, Wenjing; Liao, Xiang; Li, Jin; Yang, Chen; Qin, Han; Wang, Meng; Ding, Ran; Li, Ruijie; Jian, Tingliang; Wang, Yanhong; Zhang, Jianxiong; Yang, Zhiqi; Jin, Wenjun; Qin, Song; Lu, Ya-Cheng; Chen, Tao; Stobart, Jillian; Weber, Bruno; Adelsberger, Helmuth; Konnerth, Arthur; Chen, Xiaowei

doi:10.1038/s41593-021-00949-8

Cited by 49 publications

(45 citation statements)

References 59 publications

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“…Disturbances in the underlying neural circuitry of fear response are associated with phobias or post-traumatic stress disorder (PTSD) (Herry et al (2010)). We did not see changes in Disturbances in ACh signaling in neurons or glia in hippocampus, amygdala and mPFC were found in cue encoding, spatial processing, aversive learning, extinction, and fear renewal (Likhtik and Johansen (2019), Yanpallewar et al (2022), Zhang et al (2021), Lotfipour et al (2013), Lotfipour et al (2017), Kutlu et al (2018) 2020)). For example, feed-forward inhibition from the ventral hippocampus to PL is sufficient to decrease contextual fear renewal, while feed-forward inhibition from ventral hippocampus to IL increases fear renewal (Marek et al (2018), Vasquez et al (2019).…”

Section: Role Of Gaba Co-transmission In Fear Renewalmentioning

confidence: 67%

Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions

Goral

Harper

Bernstein

et al. 2022

Preprint

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Altered signaling or function of acetylcholine (ACh) has been reported in various neurological diseases, including Alzheimer's disease, Tourette syndrome, epilepsy among others. Many neurons that release ACh also co-transmit the neurotransmitter gamma-aminobutyrate (GABA) at synapses in the hippocampus, striatum, and medial prefrontal cortex (mPFC). Although ACh transmission is crucial for higher brain functions such as learning and memory, the role of co-transmitted GABA from ACh neurons in brain function remains unknown. Thus, the overarching goal of this study was to investigate how a systemic loss of GABA co-transmission from ACh neurons affected the behavioral performance of mice. To do this, we used a conditional knock-out mouse of the vesicular GABA transporter (vGAT) crossed with the ChAT-Cre driver line to selectively ablate GABA co-transmission at ACh synapses. In a comprehensive series of standardized behavioral assays, we compared Cre-negative control mice with Cre-positive vGAT knock-out mice of both sexes. Loss of GABA co-transmission from ACh neurons did not disrupt the animal's sociability, motor skills or sensation. However, in the absence of GABA co-transmission, we found significant alterations in social, spatial and fear memory as well as a reduced reliance on striatum-dependent response strategies in a T-maze. In addition, male CKO mice showed increased locomotion. Taken together, the loss of GABA co-transmission leads to deficits in higher brain functions and behaviors. Therefore, we propose that ACh/GABA co-transmission modulates neural circuitry involved in the affected behaviors.

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Section: Role Of Gaba Co-transmission In Fear Renewalmentioning

confidence: 67%

Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions

Goral

Harper

Bernstein

et al. 2022

Preprint

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“…Furthermore, this evidence highlights the importance of nociception in shaping the activity of brain cortical circuits and hence the behavior. In this case, Zhang et al (2021) showed that footshock-evoked calcium activity in auditory cortical astrocytes is induced in fear memory and its extinction goes in parallel with the extinction of the behavior.…”

Section: Introductionmentioning

confidence: 87%

“…Noxious stimulation (footshock) can induce reliable calcium activity in astrocytes in other brain areas related to pain perception such as the hippocampus ( Zhang et al, 2021 ). Moreover, auditory cortical astrocytes are more responsive to footshock (67%) in comparison to the number of astrocytes activated by the natural sensory stimuli, sound (8%).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, auditory cortical astrocytes are more responsive to footshock (67%) in comparison to the number of astrocytes activated by the natural sensory stimuli, sound (8%). Here, astrocytes respond with a coordinated large-scale activity that is partially mediated by gap junctions and depends on the nicotinic acetylcholine receptors ( Zhang et al, 2021 ). This supports the relevant role of neuromodulatory systems in mediating nociceptive-evoked responses in astrocytes throughout the nervous system.…”

Section: Introductionmentioning

confidence: 99%

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From nociception to pain perception, possible implications of astrocytes

Higinio-Rodríguez

Rivera-Villaseñor

Calero-Vargas

et al. 2022

Front. Cell. Neurosci.

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Astrocytes are determinants for the functioning of the CNS. They respond to neuronal activity with calcium increases and can in turn modulate synaptic transmission, brain plasticity as well as cognitive processes. Astrocytes display sensory-evoked calcium responses in different brain structures related to the discriminative system of most sensory modalities. In particular, noxious stimulation evoked calcium responses in astrocytes in the spinal cord, the hippocampus, and the somatosensory cortex. However, it is not clear if astrocytes are involved in pain. Pain is a private, personal, and complex experience that warns us about potential tissue damage. It is a perception that is not linearly associated with the amount of tissue damage or nociception; instead, it is constructed with sensory, cognitive, and affective components and depends on our previous experiences. However, it is not fully understood how pain is created from nociception. In this perspective article, we provide an overview of the mechanisms and neuronal networks that underlie the perception of pain. Then we proposed that coherent activity of astrocytes in the spinal cord and pain-related brain areas could be important in binding sensory, affective, and cognitive information on a slower time scale.

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“…Modulation of neuronal plasticity is a plausible candidate for such a process, since it acts on behavioral timescales 57 and takes place upon salient events 58 . Such modulation has been studied for hippocampal and other astrocytes both in vitro [59][60][61] and more recently also in vivo [62][63][64][65][66] . It remains open what output signals may be triggered by somatic activation of astrocytes, potentially instantiating feedback modulation of the surrounding neuronal processes.…”

Section: A Role For Astrocytes To Slowly Process Past Eventsmentioning

confidence: 99%

Centripetal integration of past events by hippocampal astrocytes and its regulation by the locus coeruleus

Rupprecht

Lewis

Helmchen

2022

Preprint

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An essential feature of neurons is their ability to centrally integrate information from their dendrites. The activity of astrocytes, on the other hand, has been described to be mostly uncoordinated across the cellular compartments and therefore without central integration. Here, we describe conditional centripetal integration, a principle how astrocytes integrate calcium signals from their distal processes. We performed calcium imaging of hippocampal astrocytes and neurons in head-fixed mice, together with monitoring of body movements and pupil diameter. Global astrocytic activity was well explained by the concurrent pupil diameter as a proxy for arousal, but equally well as leaky integration of past neuronal and behavioral events on a timescale of seconds. This integration of past events occurred in a centripetal pattern in individual astrocytes, starting in distal processes followed by a slow propagation towards the soma. Centripetal propagation was facilitated by high levels of arousal but impeded when pre-event calcium levels were high. Together, our results establish astrocytes as computational units of the brain that slowly and conditionally integrate information about the past.

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Fear learning induces α7-nicotinic acetylcholine receptor-mediated astrocytic responsiveness that is required for memory persistence

Cited by 49 publications

References 59 publications

Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions

Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions

From nociception to pain perception, possible implications of astrocytes

Centripetal integration of past events by hippocampal astrocytes and its regulation by the locus coeruleus

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