scholarly journals Muscarinic and Nicotinic Modulation of Neocortical Layer 6A Synaptic Microcircuits Is Cooperative and Cell-Specific

2019 ◽  
Vol 30 (6) ◽  
pp. 3528-3542 ◽  
Author(s):  
Danqing Yang ◽  
Robert Günter ◽  
Guanxiao Qi ◽  
Gabriele Radnikow ◽  
Dirk Feldmeyer
Keyword(s):  
Differential Expression ◽  
Somatosensory Cortex ◽  
Pyramidal Cell ◽  
Glutamate Release ◽  
Synaptic Connections ◽  
Presynaptic Neuron ◽  
Synaptic Release ◽  
Low Concentrations ◽  
Behavioral States ◽  
Ach Receptors

Abstract Acetylcholine (ACh) is known to regulate cortical activity during different behavioral states, for example, wakefulness and attention. Here we show a differential expression of muscarinic ACh receptors (mAChRs) and nicotinic ACh receptors (nAChRs) in different layer 6A (L6A) pyramidal cell (PC) types of somatosensory cortex. At low concentrations, ACh induced a persistent hyperpolarization in corticocortical (CC) but a depolarization in corticothalamic (CT) L6A PCs via M 4 and M1 mAChRs, respectively. At ~ 1 mM, ACh depolarized exclusively CT PCs via α4β2 subunit-containing nAChRs without affecting CC PCs. Miniature EPSC frequency in CC PCs was decreased by ACh but increased in CT PCs. In synaptic connections with a presynaptic CC PC, glutamate release was suppressed via M4 mAChR activation but enhanced by nAChRs via α4β2 nAChRs when the presynaptic neuron was a CT PC. Thus, in L6A, the interaction of mAChRs and nAChRs results in an altered excitability and synaptic release, effectively strengthening CT output while weakening CC synaptic signaling.

scholarly journals Cell Type-Specific Modulation of Layer 6A Excitatory Microcircuits by Acetylcholine in Rat Barrel Cortex

2019 ◽  
Author(s):  
Danqing Yang ◽  
Robert Günter ◽  
Guanxiao Qi ◽  
Gabriele Radnikow ◽  
Dirk Feldmeyer
Keyword(s):  
Pyramidal Cell ◽  
Barrel Cortex ◽  
Glutamate Release ◽  
Synaptic Connections ◽  
Cell Type ◽  
Presynaptic Neuron ◽  
Synaptic Release ◽  
Low Concentrations ◽  
Cell Type Specific ◽  
Behavioral States

AbstractAcetylcholine (ACh) is known to regulate cortical activity during different behavioral states, e.g. wakefulness and attention. Here we show a differential expression of muscarinic ACh receptors (mAChRs) and nicotinic AChRs (nAChRs) in different layer 6A (L6A) pyramidal cell (PC) types of somatosensory cortex. At low concentrations, ACh induced a persistent hyperpolarization in corticocortical (CC) but a depolarization in corticothalamic (CT) L6A PCs via M4 and M1 mAChRs, respectively. At ∼1 mM ACh depolarized exclusively CT PCs via α4β2 subunit-containing nAChRs without affecting CC PCs. Miniature EPSC frequency in CC PCs was decreased by ACh but increased in CT PCs. In synaptic connections with a presynaptic CC PC, glutamate release was suppressed via M4 mAChR activation but enhanced by nAChRs via α4β2 nAChRs when the presynaptic neuron was a CT PC. Thus, in layer 6A the interaction of mAChRs and nAChRs results in an altered excitability and synaptic release, effectively strengthening corticothalamic output while weakening corticocortical synaptic signaling.

Reverse Optical Trawling for Synaptic Connections In Situ

2009 ◽  
Vol 102 (1) ◽  
pp. 636-643 ◽  
Author(s):  
Takuya Sasaki ◽  
Genki Minamisawa ◽  
Naoya Takahashi ◽  
Norio Matsuki ◽  
Yuji Ikegaya
Keyword(s):  
Network Connectivity ◽  
Synaptic Activity ◽  
Calcium Transients ◽  
Synaptic Connections ◽  
False Positive Error ◽  
Presynaptic Neuron ◽  
Promising Tool ◽  
On Line ◽  
False Positive Error Rate ◽  
Presynaptic Neurons

We introduce a new method to unveil the network connectivity among dozens of neurons in brain slice preparations. While synaptic inputs were whole cell recorded from given postsynaptic neurons, the spatiotemporal firing patterns of presynaptic neuron candidates were monitored en masse with functional multineuron calcium imaging, an optical technique that records action potential–evoked somatic calcium transients with single-cell resolution. By statistically screening the neurons that exhibited calcium transients immediately before the postsynaptic inputs, we identified the presynaptic cells that made synaptic connections onto the patch-clamped neurons. To enhance the detection power, we devised the following points: 1) [K+]e was lowered and [Ca2+]e and [Mg2+]e were elevated, to reduce background synaptic activity and minimize the failure rate of synaptic transmission; and 2) a small fraction of presynaptic neurons was specifically activated by glutamate applied iontophoretically through a glass pipette that was moved to survey the presynaptic network of interest (“trawling”). Then we could theoretically detect 96% of presynaptic neurons activated in the imaged regions with a 1% false-positive error rate. This on-line probing technique would be a promising tool in the study of the wiring topography of neuronal circuits.

scholarly journals APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Tomas Fanutza ◽  
Dolores Del Prete ◽  
Michael J Ford ◽  
Pablo E Castillo ◽  
Luciano D’Adamio
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transmitter Release ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Synaptic Release ◽  
Hippocampal Synapses ◽  
A Cell ◽  
Acute Hippocampal Slices

The amyloid precursor protein (APP), whose mutations cause familial Alzheimer’s disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a γ-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function.The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer’s disease, alterations of this synaptic role of APP could contribute to dementia.

scholarly journals Dopaminergic Suppression of Synaptic Transmission in the Lateral Entorhinal Cortex

2008 ◽  
Vol 2008 ◽  
pp. 1-14 ◽  
Author(s):  
Douglas A. Caruana ◽  
C. Andrew Chapman
Keyword(s):  
Synaptic Transmission ◽  
Entorhinal Cortex ◽  
Action Potentials ◽  
Glutamate Release ◽  
Input Resistance ◽  
Low Concentrations ◽  
Cell Current ◽  
Layer I ◽  
Current Steps ◽  
Synaptic Responses

Dopaminergic projections to the superficial layers of the lateral entorhinal cortex can modulate the strength of olfactory inputs to the region. We have found that low concentrations of dopamine facilitate field EPSPs in the entorhinal cortex, and that higher concentrations of dopamine suppress synaptic responses. Here, we have used whole-cell current clamp recordings from layer II neurons to determine the mechanisms of the suppression. Dopamine (10 to 50 μM) hyperpolarized membrane potential and reversibly suppressed the amplitude of EPSPs evoked by layer I stimulation. Both AMPA- and NMDA-mediated components were suppressed, and paired-pulse facilitation was also enhanced indicating that the suppression is mediated largely by reduced glutamate release. Blockade ofD2-like receptors greatly reduced the suppression of EPSPs. Dopamine also lowered input resistance, and reduced the number of action potentials evoked by depolarizing current steps. The drop in input resistance was mediated by activation ofD1-like receptors, and was prevented by blockingK+channels with TEA. The dopaminergic suppression of synaptic transmission is therefore mediated by aD2receptor-dependent reduction in transmitter release, and aD1receptor-dependent increase in aK+conductance. This suppression of EPSPs may dampen the strength of sensory inputs during periods of elevated mesocortical dopamine activity.

scholarly journals Presynaptic CK2 promotes synapse organization and stability by targeting Ankyrin2

2014 ◽  
Vol 204 (1) ◽  
pp. 77-94 ◽  
Author(s):  
Victoria Bulat ◽  
Melanie Rast ◽  
Jan Pielage
Keyword(s):  
Kinase Activity ◽  
Complex Stability ◽  
Synaptic Connections ◽  
Metabolic Signaling ◽  
Presynaptic Nerve Terminal ◽  
Synaptic Release ◽  
Synapse Maintenance ◽  
And Function ◽  
Α Subunits

The precise regulation of synapse maintenance is critical to the development and function of neuronal circuits. Using an in vivo RNAi screen targeting the Drosophila kinome and phosphatome, we identify 11 kinases and phosphatases controlling synapse stability by regulating cytoskeletal, phospholipid, or metabolic signaling. We focus on casein kinase 2 (CK2) and demonstrate that the regulatory (β) and catalytic (α) subunits of CK2 are essential for synapse maintenance. CK2α kinase activity is required in the presynaptic motoneuron, and its interaction with CK2β, mediated cooperatively by two N-terminal residues of CK2α, is essential for CK2 holoenzyme complex stability and function in vivo. Using genetic and biochemical approaches we identify Ankyrin2 as a key presynaptic target of CK2 to maintain synapse stability. In addition, CK2 activity controls the subcellular organization of individual synaptic release sites within the presynaptic nerve terminal. Our study identifies phosphorylation of structural synaptic components as a compelling mechanism to actively control the development and longevity of synaptic connections.

Cobalt ions inhibit negative feedback in the outer retina by blocking hemichannels on horizontal cells

2004 ◽  
Vol 21 (4) ◽  
pp. 501-511 ◽  
Author(s):  
I. FAHRENFORT ◽  
T. SJOERDSMA ◽  
H. RIPPS ◽  
M. KAMERMANS
Keyword(s):  
Negative Feedback ◽  
Glutamate Release ◽  
Horizontal Cell ◽  
Activation Function ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Small Shift ◽  
Cobalt Ions ◽  
Low Concentrations ◽  
Spectral Coding

In goldfish, negative feedback from horizontal cells to cones shifts the activation function of the Ca2+ current of the cones to more negative potentials. This shift increases the amount of Ca2+ flowing into the cones, resulting in an increase in glutamate release. The increased glutamate release forms the basis of the feedback-mediated responses in second-order neurons, such as the surround-induced responses of bipolar cells and the spectral coding of horizontal cells. Low concentrations of Co2+ block these feedback-mediated responses in turtle retina. The mechanism by which this is accomplished is unknown. We studied the effects of Co2+ on the cone/horizontal network of goldfish retina and found that Co2+ greatly reduced the feedback-mediated responses in both cones and horizontal cells in a GABA-independent way. The reduction of the feedback-mediated responses is accompanied by a small shift of the Ca2+ current of the cones to positive potentials. We have previously shown that hemichannels on the tips of the horizontal cell dendrites are involved in the modulation of the Ca2+ current in cones. Both the absence of this Co2+-induced shift of the Ca2+ current in the absence of a hemichannel conductance and the sensitivity of Cx26 hemichannels to low concentrations of Co2+ are consistent with a role for hemichannels in negative feedback from horizontal cells to cones.

scholarly journals Inhibitors of asparagine-linked oligosaccharide processing alter the kinetics of the nicotinic acetylcholine receptor.

1989 ◽  
Vol 93 (5) ◽  
pp. 765-783 ◽  
Author(s):  
M Covarrubias ◽  
C Kopta ◽  
J H Steinbach
Keyword(s):  
Single Channel ◽  
Response Curves ◽  
Nicotinic Acetylcholine ◽  
Low Concentrations ◽  
Oligosaccharide Processing ◽  
Processing Step ◽  
Single Channel Currents ◽  
Channel Currents ◽  
Kinetics Of ◽  
Ach Receptors

We used selective inhibitors of the asparagine-linked oligosaccharide processing pathway to study the effect of sugar trimming on the functional properties of the nicotinic acetylcholine (ACh) receptor expressed in clonal mammalian BC3H-1 cells. Inhibitors of initial steps of the processing pathway (1-deoxynojirimycin[DNJ] and castanospermine[CS]) reduced the density of ACh receptors on the cell surface (3- to 5-fold) but their responsiveness to ACh was more reduced (5- to 10-fold). These results suggest that the function of the ACh receptor was altered. When the ACh receptors were expressed in the presence of DNJ or CS, analysis of ACh-evoked single-channel currents (-100 mV and 11 degrees C) revealed an approximate threefold reduction in the opening rate (control: 600-650 s(-1)), treated: 130-250 s(-1)) and an approximate twofold reduction in the rate of agonist dissociation (control: 900-1,000 s(-1), treated: 400-500 s(-1)). In addition, the proportion of brief duration bursts (tau = 50-100 microseconds) was increased (1.5- to 2-fold) by treatments with DNJ or CS. In contrast, an inhibitor of a late processing step (swainsonine) did not produce such alterations. The single-channel conductance was not altered by any of the three inhibitors, and the slopes of log-log dose-response curves at low concentrations and desensitization did not appear to be affected. Each inhibitor altered the electrophoretic mobility of the ACh receptor subunits. We conclude that early sugar trimming can influence the kinetics of the nicotinic ACh receptor in BC3H-1 cells.

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