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Slow and fast cortical cholinergic arousal is reduced in a mouse model of focal seizures with impaired consciousness.
Cell Rep
December 2024
Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address:
Article Synopsis
- Patients with focal temporal lobe seizures often lose consciousness, showing brain activity similar to deep sleep.
- Previous studies in rats suggest that reduced arousal in the brain leads to decreased brain function during these seizures, but they didn't connect this to conscious behavior.
- In this study using awake mice, researchers found that seizures affect behavior, particularly responses to sounds, by altering acetylcholine levels in the brain, highlighting the link between reduced brain activity and loss of consciousness during these episodes.
In vivo AAV9-Myo7a gene rescue restores hearing and cholinergic efferent innervation in inner hair cells.
JCI Insight
December 2024
School of Biosciences, University of Sheffield, Sheffield, United Kingdom.
In the mammalian cochlea, sensory hair cells are crucial for the transduction of acoustic stimuli into electrical signals, which are then relayed to the central auditory pathway via spiral ganglion neuron (SGN) afferent dendrites. The SGN output is directly modulated by inhibitory cholinergic axodendritic synapses from the efferent fibers originating in the superior olivary complex. When the adult cochlea is subjected to noxious stimuli or aging, the efferent system undergoes major rewiring, such that it reestablishes direct axosomatic contacts with the inner hair cells (IHCs), which occur only transiently during prehearing stages of development.
View Article and Find Full Text PDFAging is associated with dysfunction in the cholinergic system, including degeneration of basal forebrain cholinergic terminals that innervate the cortex, which directly contributes to age- and disease-related cognitive decline. In this study, we used [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) imaging to assess the effect of age on cholinergic terminal integrity in predefined regions of interest and its relationship to cognitive performance in healthy older adults who underwent neuropsychological assessment and FEOBV PET brain imaging. Our results showed age-related reductions in FEOBV binding, particularly in the anterior cingulate cortex-our primary region of interest-as well as in the striatum, posterior cingulate cortex, and primary auditory cortex.
View Article and Find Full Text PDFAlpha-2 nicotinic acetylcholine receptors regulate spectral integration in auditory cortex.
Front Neural Circuits
November 2024
Department of Neurobiology and Behavior, Center for Hearing Research, University of California, Irvine, Irvine, CA, United States.
Introduction: In primary auditory cortex (A1), nicotinic acetylcholine receptors (nAChRs) containing α2 subunits are expressed in layer 5 Martinotti cells (MCs)-inhibitory interneurons that send a main axon to superficial layers to inhibit distal apical dendrites of pyramidal cells (PCs). MCs also contact interneurons in supragranular layers that, in turn, inhibit PCs. Thus, MCs may regulate PCs via inhibition and disinhibition, respectively, of distal and proximal apical dendrites.
View Article and Find Full Text PDFConductance properties of the α9α10 nicotinic acetylcholine receptor of neonatal mouse inner and outer hair cells.
Hear Res
November 2024
School of Life Sciences, Keele University, ST5 5BG, UK. Electronic address:
In the developing cochlea, just before the onset of hearing on postnatal day 12, the medial olivocochlear efferent axons in synaptic contact with the inner hair cells (IHCs) start withdrawing and new efferent synaptic connections are formed on the outer hair cells (OHCs), thereby progressing towards the adult pattern of medial olivocochlear efferent innervation. The synapses are inhibitory, calcium influx through the α9α10 nicotinic acetylcholine receptors (nAChRs) driving opening of calcium-dependent potassium channels. The nAChRs appear to function similarly in IHCs and OHCs, although with probable kinetic differences.
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