scholarly journals Synaptic release of acetylcholine rapidly suppresses cortical activity by recruiting muscarinic receptors in layer 4

2018 ◽  
Author(s):  
Rajan Dasgupta ◽  
Frederik Seibt ◽  
Michael Beierlein

AbstractBasal forebrain (BF) cholinergic projections to neocortex dynamically regulate information processing. However, the underlying synaptic and cellular mechanisms remain poorly understood. While synaptically released acetylcholine (ACh) can recruit nicotinic ACh receptors (nAChRs) expressed in distinct types of interneurons, previous work has not defined a clear role for muscarinic ACh receptors (mAChRs) in the fast cholinergic control of cortical activity. To address this question, we employed a slice model of cortical activity and used optogenetics to selectively activate cholinergic afferents. We found that transient ACh increases led to a rapid and persistent suppression of cortical activity, mediated by mAChRs in layer 4 and by nAChRs in layer 2/3. Furthermore, mAChR-dependent cholinergic control was mediated at least in part by a short-latency and long-lasting inhibition of layer 4 excitatory neurons. Thus, the activation of postsynaptic mAChRs is central to the flexible cholinergic control of cortical activity.

2004 ◽  
Vol 124 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Heidi S. Phillips ◽  
Merry Nishimura ◽  
Mark P. Armanini ◽  
Karen Chen ◽  
Kathryn M. Albers ◽  
...  

2011 ◽  
Vol 105 (1) ◽  
pp. 347-355 ◽  
Author(s):  
Giao B. Hang ◽  
Yang Dan

Neocortical neurons in vivo receive concurrent synaptic inputs from multiple sources, including feedforward, horizontal, and feedback pathways. Layer 2/3 of the visual cortex receives feedforward input from layer 4 and horizontal input from layer 2/3. Firing of the pyramidal neurons, which carries the output to higher cortical areas, depends critically on the interaction of these pathways. Here we examined synaptic integration of inputs from layer 4 and layer 2/3 in rat visual cortical slices. We found that the integration is sublinear and temporally asymmetric, with larger responses if layer 2/3 input preceded layer 4 input. The sublinearity depended on inhibition, and the asymmetry was largely attributable to the difference between the two inhibitory inputs. Interestingly, the asymmetric integration was specific to pyramidal neurons, and it strongly affected their spiking output. Thus via cortical inhibition, the temporal order of activation of layer 2/3 and layer 4 pathways can exert powerful control of cortical output during visual processing.


2009 ◽  
Vol 101 (4) ◽  
pp. 2052-2061 ◽  
Author(s):  
Ambarish S. Ghatpande ◽  
Alan Gelperin

The mammalian olfactory bulb receives multiple modulatory inputs, including a cholinergic input from the basal forebrain. Understanding the functional roles played by the cholinergic input requires an understanding of the cellular mechanisms it modulates. In an in vitro olfactory bulb slice preparation we demonstrate cholinergic muscarinic modulation of glutamate release onto granule cells that results in γ-aminobutyric acid (GABA) release onto mitral/tufted cells. We demonstrate that the broad-spectrum cholinergic agonist carbachol triggers glutamate release from mitral/tufted cells that activates both AMPA and NMDA receptors on granule cells. Activation of the granule cell glutamate receptors leads to calcium influx through voltage-gated calcium channels, resulting in spike-independent, asynchronous GABA release at reciprocal dendrodendritic synapses that granule cells form with mitral/tufted cells. This cholinergic modulation of glutamate release persists through much of postnatal bulbar development, suggesting a functional role for cholinergic inputs from the basal forebrain in bulbar processing of olfactory inputs and possibly in postnatal development of the olfactory bulb.


Induced fission track techniques permit us to determine quantitatively the microscopic distribution of uranium in rocks, in their constituent minerals, and in percolating fluids. Both primary magmatic variations and secondary mobilization of uranium can be discerned. Concentrations of uranium in phenocrysts and fresh glasses of oceanic basalts and gabbros are very low (2-80 parts/10 9 ) and are comparable to concentrations in the same minerals of the associated ultramafic rocks. Variations with depth in D.S.D.P. holes show several distinct cyclic variations of uranium, accompanied by parallel trends in some major and trace elements. In Hole 332B (mid-Atlantic ridge, 36 °N), uranium and other elements can be shown to fall into two distinct groupings, each group following its own characteristic fractionation trend, suggesting that two distinct magmas differentiated independently beneath the median valley, the two magmas alternating in their contribution to the formation of oceanic layer 2. Earlier investigations of the uranium distribution in surface pillows and other dredged rocks exposed to sea water had shown that, owing to halmyrolysis, the uranium concentration increases systematically with distance from the axis of a midoceanic ridge. Subsequent investigations on rocks drilled from horizons deeper into oceanic layer 2 indicate that secondary enrichment or redistribution of uranium is confined to specific zones of altered basalt, near fractures, pillow and flow margins, and especially along horizontal planes of breccias and sediments in between massive flow where convective water circulation is thought to occur. Ultramafic rocks from the base of layer 3 and top of layer 4 are also enriched in uranium when hydrated by sea water during the process of serpentinization. A combination of these processes may double the uranium content of an oceanic lithospheric plate between the time of its formation and its eventual subduction.


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