scholarly journals Activity-dependent modulation of NMDA receptors by endogenous zinc shapes dendritic function in cortical neurons.

2021 ◽  
Author(s):  
Annunziato Morabito ◽  
Yann Zerlaut ◽  
Benjamin Serraz ◽  
Romain Sala ◽  
Pierre Paoletti ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Cortical Neurons ◽  
Single Neuron ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Cortical Circuits ◽  
New Perspective ◽  
Activity Dependent

Activation of NMDA receptors (NMDARs) has been proposed to be a key component of single neuron computations in vivo. However is unknown if specific mechanisms control the function of such receptors and modulate input-output transformations performed by cortical neurons under in vivo-like conditions. Here we found that in layer 2/3 pyramidal neurons (L2/3 PNs), repeated synaptic stimulation results in an activity-dependent decrease in NMDARs activity by vesicular zinc. Such a mechanism shifted the threshold for dendritic non-linearities and strongly reduced LTP induction. Modulation of NMDARs was cell- and pathway-specific, being present selectively in L2/3-L2/3 connections but absent in ascending bottom-up inputs originating from L4 neurons. Numerical simulations highlighted that activity-dependent modulation of NMDARs has an important influence in dendritic computations endowing L2/3 PN dendrites with the ability to sustain dendritic non-linear integrations constant across different regimes of synaptic activity like those found in vivo. The present results therefore provide a new perspective on the action of vesicular zinc in cortical circuits by highlighting the role of this endogenous ion in normalizing dendritic integration of PNs during a constantly changing synaptic input pattern.

scholarly journals Spatiotemporal constraints on optogenetic inactivation in cortical circuits

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Nuo Li ◽  
Susu Chen ◽  
Zengcai V Guo ◽  
Han Chen ◽  
Yan Huo ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Inhibitory Neurons ◽  
Dependent Manner ◽  
Cortical Circuits ◽  
Neuronal Populations ◽  
Multiple Length Scales ◽  
Dose Dependent ◽  
Reduced Activity

Optogenetics allows manipulations of genetically and spatially defined neuronal populations with excellent temporal control. However, neurons are coupled with other neurons over multiple length scales, and the effects of localized manipulations thus spread beyond the targeted neurons. We benchmarked several optogenetic methods to inactivate small regions of neocortex. Optogenetic excitation of GABAergic neurons produced more effective inactivation than light-gated ion pumps. Transgenic mice expressing the light-dependent chloride channel GtACR1 produced the most potent inactivation. Generally, inactivation spread substantially beyond the photostimulation light, caused by strong coupling between cortical neurons. Over some range of light intensity, optogenetic excitation of inhibitory neurons reduced activity in these neurons, together with pyramidal neurons, a signature of inhibition-stabilized neural networks ('paradoxical effect'). The offset of optogenetic inactivation was followed by rebound excitation in a light dose-dependent manner, limiting temporal resolution. Our data offer guidance for the design of in vivo optogenetics experiments.

In vivo neuroprotective role of NMDA receptors against kainate-induced excitotoxicity in murine hippocampal pyramidal neurons

2003 ◽  
Vol 85 (5) ◽  
pp. 1336-1346 ◽  
Author(s):  
Kiyokazu Ogita ◽  
Hiroaki Okuda ◽  
Yasuhiro Yamamoto ◽  
Norito Nishiyama ◽  
Yukio Yoneda
Keyword(s):  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Pyramidal Neurons

Impact of Spontaneous Synaptic Activity on the Resting Properties of Cat Neocortical Pyramidal Neurons In Vivo

1998 ◽  
Vol 79 (3) ◽  
pp. 1450-1460 ◽  
Author(s):  
Denis Paré ◽  
Eric Shink ◽  
Hélène Gaudreau ◽  
Alain Destexhe ◽  
Eric J. Lang
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Intact Brain ◽  
Lower Temperature ◽  
The Impact ◽  
Neocortical Pyramidal Neurons

Paré, Denis, Eric Shink, Hélène Gaudreau, Alain Destexhe, and Eric J. Lang. Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons in vivo. J. Neurophysiol. 79: 1450–1460, 1998. The frequency of spontaneous synaptic events in vitro is probably lower than in vivo because of the reduced synaptic connectivity present in cortical slices and the lower temperature used during in vitro experiments. Because this reduction in background synaptic activity could modify the integrative properties of cortical neurons, we compared the impact of spontaneous synaptic events on the resting properties of intracellularly recorded pyramidal neurons in vivo and in vitro by blocking synaptic transmission with tetrodotoxin (TTX). The amount of synaptic activity was much lower in brain slices (at 34°C), as the standard deviation of the intracellular signal was 10–17 times lower in vitro than in vivo. Input resistances ( R ins) measured in vivo during relatively quiescent epochs (“control R ins”) could be reduced by up to 70% during periods of intense spontaneous activity. Further, the control R ins were increased by ∼30–70% after TTX application in vivo, approaching in vitro values. In contrast, TTX produced negligible R in changes in vitro (∼4%). These results indicate that, compared with the in vitro situation, the background synaptic activity present in intact networks dramatically reduces the electrical compactness of cortical neurons and modifies their integrative properties. The impact of the spontaneous synaptic bombardment should be taken into account when extrapolating in vitro findings to the intact brain.

scholarly journals Widely Different Correlation Patterns Between Pairs of Adjacent Thalamic Neurons In vivo

2021 ◽  
Vol 15 ◽  
Author(s):  
Anders Wahlbom ◽  
Hannes Mogensen ◽  
Henrik Jörntell
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Thalamic Nuclei ◽  
Thalamic Neurons ◽  
Low Weight ◽  
Afferent Inputs ◽  
Cortical Inputs ◽  
Unique Relationship ◽  
Spike Firing

We have previously reported different spike firing correlation patterns among pairs of adjacent pyramidal neurons within the same layer of S1 cortex in vivo, which was argued to suggest that acquired synaptic weight modifications would tend to differentiate adjacent cortical neurons despite them having access to near-identical afferent inputs. Here we made simultaneous single-electrode loose patch-clamp recordings from 14 pairs of adjacent neurons in the lateral thalamus of the ketamine-xylazine anesthetized rat in vivo to study the correlation patterns in their spike firing. As the synapses on thalamic neurons are dominated by a high number of low weight cortical inputs, which would be expected to be shared for two adjacent neurons, and as far as thalamic neurons have homogenous membrane physiology and spike generation, they would be expected to have overall similar spike firing and therefore also correlation patterns. However, we find that across a variety of thalamic nuclei the correlation patterns between pairs of adjacent thalamic neurons vary widely. The findings suggest that the connectivity and cellular physiology of the thalamocortical circuitry, in contrast to what would be expected from a straightforward interpretation of corticothalamic maps and uniform intrinsic cellular neurophysiology, has been shaped by learning to the extent that each pair of thalamic neuron has a unique relationship in their spike firing activity.

Opposing roles for neurotrophin-3 in targeting and collateral formation of distinct sets of developing cortical neurons

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3335-3345
Author(s):  
V. Castellani ◽  
J. Bolz
Keyword(s):  
Cortical Neurons ◽  
Developmental Stages ◽  
Axonal Guidance ◽  
Cortical Circuits ◽  
Axonal Branching ◽  
Guidance Cue ◽  
Neurotrophin 3 ◽  
Cortical Membranes ◽  
Opposing Effects

Neurotrophin-3 and its receptor TrkC are expressed during the development of the mammalian cerebral cortex. To examine whether neurotrophin-3 might play a role in the elaboration of layer-specific cortical circuits, slices of layer 6 and layers 2/3 neurons were cultured in the presence of exogenously applied neurotrophin-3. Results indicate that neurotrophin-3 promotes axonal branching of layer 6 axons, which target neurotrophin-3-expressing layers in vivo, and that it inhibits branching of layers 2/3 axons, which avoid neurotrophin-3-expressing layers. Such opposing effects of neurotrophin-3 on axonal branching were also observed with embryonic cortical neurons, indicating that the response to neurotrophin-3 is specified at early developmental stages, prior to cell migration. In addition to its effects on fiber branching, axonal guidance assays also indicate that neurotrophin-3 is an attractive signal for layer 6 axons and a repellent guidance cue for layers 2/3 axons. Experiments with specific antibodies to neutralize neurotrophin-3 in cortical membranes revealed that endogenous levels of neurotrophin-3 are sufficient to regulate branching and targeting of cortical axons. These opposing effects of neurotrophin-3 on specific populations of axons demonstrate that it could serve as one of the signals for the elaboration of local cortical circuits.

Dynorphin A Elicits an Increase in Intracellular Calcium in Cultured Neurons Via a Non-Opioid, Non-NMDA Mechanism

2000 ◽  
Vol 83 (5) ◽  
pp. 2610-2615 ◽  
Author(s):  
Qingbo Tang ◽  
Ronald M. Lynch ◽  
Frank Porreca ◽  
Josephine Lai
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Intracellular Calcium ◽  
Cortical Neurons ◽  
Excitatory Amino Acid ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Dynorphin A ◽  
Excitatory Effect

The opioid peptide dynorphin A is known to elicit a number of pathological effects that may result from neuronal excitotoxicity. An up-regulation of this peptide has also been causally related to the dysesthesia associated with inflammation and nerve injury. These effects of dynorphin A are not mediated through opioid receptor activation but can be effectively blocked by pretreatment with N-methyl-d-aspartate (NMDA) receptor antagonists, thus implicating the excitatory amino acid system as a mediator of the actions of dynorphin A and/or its fragments. A direct interaction between dynorphin A and the NMDA receptors has been well established; however the physiological relevance of this interaction remains equivocal. This study examined whether dynorphin A elicits a neuronal excitatory effect that may underlie its activation of the NMDA receptors. Calcium imaging of individual cultured cortical neurons showed that the nonopioid peptide dynorphin A(2-17) induced a time- and dose-dependent increase in intracellular calcium. This excitatory effect of dynorphin A(2-17) was insensitive to (+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a,d]-cyclohepten-5,10-imine (MK-801) pretreatment in NMDA-responsive cells. Thus dynorphin A stimulates neuronal cells via a nonopioid, non-NMDA mechanism. This excitatory action of dynorphin A could modulate NMDA receptor activity in vivo by enhancing excitatory neurotransmitter release or by potentiating NMDA receptor function in a calcium-dependent manner. Further characterization of this novel site of action of dynorphin A may provide new insight into the underlying mechanisms of dynorphin excitotoxicity and its pathological role in neuropathy.

scholarly journals Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Philip Hasel ◽  
Owen Dando ◽  
Zoeb Jiwaji ◽  
Paul Baxter ◽  
Alison C. Todd ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Synaptic Activity ◽  
Rna Seq ◽  
Metabolic Cooperation ◽  
Closely Related Species ◽  
Lactate Shuttle ◽  
Activity Dependent ◽  
Elevated Lactate

Abstract The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte–neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte–neuron metabolic cooperation.

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