synaptic integration
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2021 ◽  
pp. JN-RM-0035-21
Author(s):  
Emily Church ◽  
Edaeni Hamid ◽  
Zack Zurawski ◽  
Mariana Potcoava ◽  
Eden Flores-Barrera ◽  
...  

Cell Reports ◽  
2021 ◽  
Vol 37 (12) ◽  
pp. 110133
Author(s):  
Roman Serrat ◽  
Ana Covelo ◽  
Vladimir Kouskoff ◽  
Sebastien Delcasso ◽  
Andrea Ruiz-Calvo ◽  
...  
Keyword(s):  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Celia Biane ◽  
Florian Rückerl ◽  
Therese Abrahamsson ◽  
Cécile Saint-Cloment ◽  
Jean Mariani ◽  
...  

Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits.


eNeuro ◽  
2021 ◽  
pp. ENEURO.0235-21.2021
Author(s):  
Christopher Dorsett ◽  
Benjamin D. Philpot ◽  
Spencer LaVere Smith ◽  
Ikuko T. Smith

2021 ◽  
Author(s):  
Simonas Griesius ◽  
Cian O'Donnell ◽  
Sophie Waldron ◽  
Kerrie L Thomas ◽  
Dominic M Dwyer ◽  
...  

Background: Genetic variations indicating loss of function in the DLG2 gene have been associated with markedly increased risk for schizophrenia, autism spectrum disorder, and intellectual disability. DLG2 encodes the postsynaptic scaffolding protein DLG2 (PSD93) that interacts with NMDA receptors, potassium channels, and cytoskeletal regulators but the net impact of these interactions on synaptic plasticity, likely underpinning cognitive impairments associated with these conditions, remains unclear. Methods: Hippocampal CA1 neuronal excitability and synaptic function were investigated in a novel clinically relevant heterozygous Dlg2+/- rat model using ex vivo patch-clamp electrophysiology, pharmacology, and computational modelling. Results: Dlg2+/- rats had increased NMDA receptor-mediated synaptic currents and, conversely, impaired associative long-term potentiation. This impairment resulted from an increase in potassium channel function leading to a decrease in input resistance and reduced supra-linear dendritic integration during induction of associative long-term potentiation. Enhancement of dendritic excitability by blockade of potassium channels or activation of muscarinic M1 receptors with selective allosteric agonist 77-LH-28- 1 reduced the threshold for dendritic integration and 77-LH-28-1 rescued the associative long- term potentiation impairment in the Dlg2+/- rats. Conclusions: Despite increasing synaptic NMDA receptor currents, the combined impact of reduced DLG2 impairs synaptic integration in dendrites resulting in disrupted associative synaptic plasticity. This biological phenotype can be reversed by compound classes used clinically such as muscarinic M1 receptor agonists and is therefore a potential target for therapeutic intervention.


2021 ◽  
Author(s):  
Rachel Humphries ◽  
Jack R. Mellor ◽  
Cian O’Donnell

AbstractAcetylcholine has been proposed to facilitate the formation of memory ensembles within the hippocampal CA3 network, by enhancing plasticity at CA3-CA3 recurrent synapses. Regenerative NMDA receptor (NMDAR) activation in CA3 neuron dendrites (NMDA spikes) increase synaptic Ca2+ influx and can trigger this synaptic plasticity. Acetylcholine inhibits potassium channels which enhances dendritic excitability and therefore could facilitate NMDA spike generation. Here, we investigate NMDAR-mediated nonlinear synaptic integration in stratum radiatum (SR) and stratum lacunosum moleculare (SLM) dendrites in a reconstructed CA3 neuron computational model and study the effect of acetylcholine on this nonlinearity. We found that distal SLM dendrites, with a higher input resistance, had a lower threshold for NMDA spike generation compared to SR dendrites. Simulating acetylcholine by blocking potassium channels (M-type, A-type, Ca2+-activated, and inwardly-rectifying) increased dendritic excitability and reduced the number of synapses required to generate NMDA spikes, particularly in the SR dendrites. The magnitude of this effect was heterogeneous across different dendritic branches within the same neuron. These results predict that acetylcholine facilitates dendritic integration and NMDA spike generation in selected CA3 dendrites which could strengthen connections between specific CA3 neurons to form memory ensembles.Highlights-Using biophysical computational models of CA3 pyramidal neurons we estimated the quantitative effects of acetylcholine on nonlinear synaptic integration.-Nonlinear NMDA spikes can be triggered by fewer synapses in distal dendrites due to increased local input resistance.-Acetylcholine broadly reduces the number of synapses needed to trigger NMDA spikes, but the magnitude of the effect varies across dendrite branches within a single neuron.-No single potassium channel type is the dominant mediator of the excitability effects of acetylcholine.


2021 ◽  
Vol 857 ◽  
pp. 158027
Author(s):  
Seungho Song ◽  
Minho Kim ◽  
Gunsang Yoo ◽  
Sung-Min Kwon ◽  
Jae-Sang Heo ◽  
...  

eNeuro ◽  
2021 ◽  
pp. ENEURO.0396-20.2020
Author(s):  
Chenguang Li ◽  
Allan T. Gulledge

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