scholarly journals Mitochondria decode firing frequency and coincidences of postsynaptic APs and EPSPs

2021 ◽  
Author(s):  
Ohad Stoler ◽  
Alexandra Stavsky ◽  
Yana Khrapunsky ◽  
Israel Melamed ◽  
Grace Stutzmann ◽  
...  

Mitochondrial metabolism is critical for brain function. However, the mechanisms linking mitochondrial energy production to neuronal activity are elusive. Using whole-cell electrical recordings from Layer 5 pyramidal neurons in cortical slices and fluorescence imaging of cytosolic, mitochondrial Ca2+ indicators and endogenous NAD(P)H, we revealed ultra-fast, spike-evoked mitochondrial Ca2+ transients temporally similar to cytosolic Ca2+ elevations. We demonstrate that, whereas single or few spikes elicit the mitochondrial Ca2+ transients throughout the cell, their amplitude is differentially regulated in distinct neuronal compartments. Thus, these signals were prominent in the soma and apical dendrites and ~3 times smaller in basal dendrites and axons. The spike firing frequency had a subtle effect on the amplitude of the cytosolic Ca2+ elevations but dramatically affected mitochondrial Ca2+ transients and NAD(P)H oxidation and recovery rates. Moreover, while subthreshold EPSPs alone caused no detectable Ca2+ elevation in dendritic mitochondria, the Hebbian coincidence of unitary EPSP and postsynaptic spike produced a localized, single mitochondrial Ca2+ elevation. These findings suggest that neuronal mitochondria are uniquely capable of decoding firing frequency and EPSP-to-spike time intervals for tuning the metabolic rate and triggering changes in synaptic efficacy.

2004 ◽  
Vol 91 (1) ◽  
pp. 324-335 ◽  
Author(s):  
H. J. Abel ◽  
J.C.F. Lee ◽  
J. C. Callaway ◽  
R. C. Foehring

We examined the effects of recent discharge activity on [Ca2+]i in neocortical pyramidal cells. Our data confirm and extend the observation that there is a linear relationship between plateau [Ca2+]i and firing frequency in soma and proximal apical dendrites. The rise in [Ca2+] activates K+ channels underlying the afterhyperpolarization (AHP), which consists of 2 Ca2+-dependent components: the medium AHP (mAHP) and the slow AHP (sAHP). The mAHP is blocked by apamin, indicating involvement of SK-type Ca2+-dependent K+ channels. The identity of the apamin-insensitive sAHP channel is unknown. We compared the sAHP and the mAHP with regard to: 1) number and frequency of spikes versus AHP amplitude; 2) number and frequency of spikes versus [Ca2+]i; 3) IAHP versus [Ca2+]i. Our data suggest that sAHP channels require an elevation of [Ca2+]i in the cytoplasm, rather than at the membrane, consistent with a role for a cytoplasmic intermediate between Ca2+ and the K+ channels. The mAHP channels appear to respond to a restricted Ca2+ domain.


1990 ◽  
Vol 64 (5) ◽  
pp. 1429-1441 ◽  
Author(s):  
O. Herreras

1. The events leading to the Schaffer collateral-induced discharge of CA1 pyramidal neurons were investigated in the hippocampus of anesthetized rats by current source-density (CSD) analysis. 2. The earliest evoked currents detected shortly after a stimulus were a sink in the zone where synapses are known to be located (300-350 microns ventral to the somatic layer) flanked by two smaller sources in the distal portion of the apical dendrites and in the somatic layer. This synaptic sink (SyS) extended over 75-100 microns; it lasted for 15-20 ms, and it reached its maximum amplitude some milliseconds after the population spike (PS) and remained in the same location. Stimuli submaximal and supramaximal for evoking a PS yielded the same pattern of current distribution for the SyS. Presynaptic fiber volleys were not detected in these recordings. 3. During the rising phase of the SyS a second sink appeared in a more proximal portion of the apical dendrites. This late dendritic sink (LS) extended over 50-75 microns and was centered 100-150 microns ventral to the somatic layer. This proximal dendritic sink was of amplitude comparable with the SyS; it outlasted the latter and was not necessarily followed by a somatic PS. The LS was extinguished with the appearance of a PS, whereas the SyS persisted regardless of the presence of a PS. 4. After maximal stimuli the LS grew until it exceeded a threshold amplitude, and then, it started to move somatopetally as a continuously propagating sink (PrS). The average speed of propagation was approximately 0.2 m/s. In 0.5-0.7 ms the PrS reached the cell-body layer displacing the passive source that moved into the basal dendrites. The PrS then became the intensive sink corresponding to the main (negative) phase of the somatic PS. This was followed by the development of an active source in the soma layer, probably corresponding to the repolarization phase of the PS. 5. From these observations it appears that the LS and PrS are active dendritic responses. It may be inferred that, shortly after the synaptic currents enter the dendrites, depolarization of adjacent membranes causes the opening of low-threshold, voltage-dependent, slowly inactivating channels that generate the LS. If the depolarization resulting from the LS current is intense enough, another population of channels open that are also voltage-dependent but of higher threshold and faster inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)


2008 ◽  
Vol 20 (1) ◽  
pp. 176-204 ◽  
Author(s):  
Nicholas V. Swindale

A mechanism is proposed by which feedback pathways model spatial patterns of feedforward activity in cortical maps. The mechanism can be viewed equivalently as readout of a content-addressable memory or as decoding of a population code. The model is based on the evidence that cortical receptive fields can often be described as a separable product of functions along several dimensions, each represented in a spatially ordered map. Given this, it is shown that for an N-dimensional map, accurate modeling and decoding of xN feedforward activity patterns can be done with Nx fibers, N of which must be active at any one time. The proposed mechanism explains several known properties of the cortex and pyramidal neurons: (1) the integration of signals by dendrites with a narrow tangential distribution, that is, apical dendrites; (2) the presence of fast-conducting feedback projections with broad tangential distributions; (3) the multiplicative effects of attention on receptive field profiles; and (4) the existence of multiplicative interactions between subthreshold feedforward inputs to basal dendrites and inputs to apical dendrites.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiyoung Park ◽  
Athanasia Papoutsi ◽  
Ryan T. Ash ◽  
Miguel A. Marin ◽  
Panayiota Poirazi ◽  
...  

AbstractPyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron’s stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron’s dendritic domains relate to its functional selectivity has not been demonstrated experimentally. We performed 2-photon dendritic micro-dissection on layer-2/3 pyramidal neurons in mouse primary visual cortex. We found that removing the apical dendritic tuft did not alter orientation-tuning. Furthermore, orientation-tuning curves were remarkably robust to the removal of basal dendrites: ablation of 2 basal dendrites was needed to cause a small shift in orientation preference, without significantly altering tuning width. Computational modeling corroborated our results and put limits on how orientation preferences among basal dendrites differ in order to reproduce the post-ablation data. In conclusion, neuronal orientation-tuning appears remarkably robust to loss of dendritic input.


1977 ◽  
Vol 25 (1) ◽  
pp. 1 ◽  
Author(s):  
CFL Hinrichsen ◽  
GE Stevens

Electron micrographs of sections of mouse neocortical layer IV, cut tangential to the pial surface, show the detailed organization of neuronal groups or 'barrels', which are related functionally to single facial vibrissae. Cortical barrels comprise 'sides' of stellate and small pyramidal neurons, groups of myelinated axons, and apical dendrites. The 'cores' comprise a neuropil of thalamic afferents, sparse neurons, converging basal dendrites of pyramidal cells and stellate cell dendrites. Some neurons of the 'sides' are attached through puncta adherentia.


2008 ◽  
Vol 99 (6) ◽  
pp. 2833-2843 ◽  
Author(s):  
Kwang-Hyun Cho ◽  
Hyun-Jong Jang ◽  
Eun-Hui Lee ◽  
Shin Hee Yoon ◽  
Sang June Hahn ◽  
...  

The effect of the cholinergic agonist carbachol (CCh) on backpropagating action potential (bAP)–evoked Ca2+ transients in distal apical and basal dendrites of layer 2/3 pyramidal neurons in the primary visual cortex of rats was studied using whole cell recordings and confocal Ca2+ imaging. In the presence of CCh (20 μM), initial bAP-evoked Ca2+ transients were followed by large propagating secondary Ca2+ transients that were restricted to proximal apical dendrites ≤40 μm from the soma. In middle apical dendrites (41–100 μm from the soma), Ca2+ transients evoked by AP bursts at 20 Hz, but not by single APs, were increased by CCh without secondary transients. CCh failed to increase the bAP-evoked Ca2+ transients in distal apical dendrites (101–270 μm from the soma). In contrast, in basal dendrites, CCh increased Ca2+ transients evoked by AP bursts, but not by single APs, and these transients were relatively constant over the entire length of the dendrites. CCh further increased the enhanced bAP-evoked Ca2+ transients in the presence of 4-aminopyridine (200 μM), an A-type K+ channel blocker, in basal and apical dendrites, except in distal apical dendrites. CCh increased large Ca2+ transients evoked by high-frequency AP bursts in basal dendrites, but not in distal apical dendrites. CCh-induced increase in Ca2+ transients was mediated by InsP3-dependent Ca2+-induced Ca2+-release. These results suggest that cholinergic stimulation differentially increases the bAP-evoked increase in [Ca2+]i in apical and basal dendrites, which may modulate synaptic activities in a location-dependent manner.


2019 ◽  
Author(s):  
Jiyoung Park ◽  
Athanasia Papoutsi ◽  
Ryan T. Ash ◽  
Miguel A. Marin ◽  
Panayiota Poirazi ◽  
...  

AbstractPyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron’s stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron’s dendritic domains relate to its functional selectivity has not been demonstrated experimentally. We performed 2-photon dendritic micro-dissection on layer-2/3 pyramidal neurons in mouse primary visual cortex. We found that removing the apical dendritic tuft did not alter orientation-tuning. Furthermore, orientation-tuning curves were remarkably robust to the removal of basal dendrites: ablation of 2-3 basal dendrites was needed to cause a small shift in orientation preference, without significantly altering tuning width. Computational modeling corroborated our results and put limits on how orientation preferences among basal dendrites differ in order to reproduce the post-ablation data. In conclusion, neuronal orientation-tuning appears remarkably robust to loss of dendritic input.


2019 ◽  
Author(s):  
EM Anderson ◽  
D Gomez ◽  
A Caccamise ◽  
D McPhail ◽  
M Hearing

AbstractExposure to unpredictable environmental stress is widely recognized as a major determinant for risk and severity in neuropsychiatric disorders such as major depressive disorder, anxiety, schizophrenia, and PTSD. The ability of ostensibly unrelated disorders to give rise to seemingly similar psychiatric phenotypes highlights a need to identify circuit-level concepts that could unify diverse factors under a common pathophysiology. Although difficult to disentangle a causative effect of stress from other factors on medial prefrontal cortex (PFC) dysfunction, a wealth of data from humans and rodents demonstrates that the PFC is a key target of stress. The present study sought to identify a model of chronic unpredictable stress (CUS) which induces affective behaviors in C57BL6J mice and once established, measure spike firing and the ability to evoke an action potential in mPFC layer 5/6 pyramidal neurons. Adult male mice received 2 weeks of ‘less intense’ stress or 2 or 4 weeks of ‘more intense’ CUS followed by sucrose preference for assessment of anhedonia, elevated plus maze for assessment of anxiety and forced swim test for assessment of depressive-like behaviors. Our findings indicate that more intense CUS exposure results in increased anhedonia, anxiety, and depressive behaviors, while the less intense stress results in no measured behavioral phenotypes. Once a behavioral model was established, mice were euthanized approximately 21 days post-stress for whole-cell patch clamp recordings from layer 5/6 pyramidal neurons in the prelimbic (PrL) and infralimbic (IL) cortices. No significant differences were initially observed in intrinsic cell excitability in either region. However, post-hoc analysis and subsequent confirmation using transgenic mice expressing tdtomato or eGFP under control of dopamine D1- or D2-type receptor showed that D1-expressing pyramidal neurons (D1-PYR) in the PrL exhibit reduced thresholds to fire an action potential (increased excitability) but impaired firing capacity at more depolarized potentials, whereas D2-expressing pyramidal neurons showed an overall reduction in excitability and spike firing frequency. Examination of synaptic transmission showed that D1- and D2-PYR in exhibit differences in basal excitatory and inhibitory signaling under naïve conditions. In CUS mice, D1-PYR showed increased frequency of both miniature excitatory and inhibitory postsynaptic currents, whereas D2-PYR only showed a reduction in excitatory currents. These findings demonstrate that the intrinsic physiology and synaptic regulation of D1- and D2-PYR subpopulations differentially undergo stress-induced plasticity that may have functional implications for stress-related pathology, and that these adaptations may reflect unique differences in basal properties regulating output of these cells.


Agriculture ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 557
Author(s):  
Roberta Barrasso ◽  
Vincenzo Tufarelli ◽  
Edmondo Ceci ◽  
Francesco Luposella ◽  
Giancarlo Bozzo

The aim of this study was to evaluate the persistence of two signs of consciousness (rhythmic breathing and corneal reflex) in lambs slaughtered according to the traditional method and Halal ritual rite. A total of 240 lambs were examined and divided into two equal groups (n = 120 each). Lambs of group A were subjected to the stunning phase by the action of an electric current on the brain, while lambs of group B were slaughtered according to the religious Halal method without prior stunning. Rhythmic breathing (RB) and corneal reflex (CR) were used as indicators of prolonged brain function, and their evaluation was carried out by the operators in three subsequent steps at 15 s, 30 s, and 90 s post-bleeding, respectively. The stunning of the lambs reduced the animal’s state of consciousness and, consequently, reduced suffering, pain, and distress. Indeed, the lambs of group B showed longer duration consciousness than the animals stunned by electrodes. The permanence of the reflexes in Halal slaughter could be reduced by introducing a reversible stunning method to make the animal temporarily unconscious. Moreover, given that our results revealed consciousness also after 90 s post-cut, the assessment of the animal’s state of consciousness in wider time intervals than those commonly used is recommended.


2009 ◽  
Vol 29 (38) ◽  
pp. 11891-11903 ◽  
Author(s):  
A. Polsky ◽  
B. Mel ◽  
J. Schiller

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