Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical
- Ben Gurion University of the Negev, Israel
- Rosalind Franklin University of Medicine and Science, United States
Abstract
Mitochondrial activity is crucial for the plasticity of central synapses, but how the firing pattern of pre- and postsynaptic neurons affects the mitochondria remains elusive. We recorded changes in the fluorescence of cytosolic and mitochondrial Ca2+ indicators in cell bodies, axons, and dendrites of cortical pyramidal neurons in mouse brain slices while evoking pre- and postsynaptic spikes. Postsynaptic spike firing elicited fast mitochondrial Ca2+ responses that were about threefold larger in the somas and apical dendrites than in basal dendrites and axons. The amplitude of these responses and metabolic activity were extremely sensitive to the firing frequency. Furthermore, while an EPSP alone caused no detectable Ca2+ elevation in the dendritic mitochondria, the coincidence of EPSP with a backpropagating spike produced prominent, highly localized mitochondrial Ca2+ hotspots. Our results indicate that mitochondria decode the spike firing frequency and the Hebbian temporal coincidences into the Ca2+ signals, which are further translated into the metabolic output and most probably lead to long-term changes in synaptic efficacy.
Data availability
A representative subset of the raw electrical recording and imaging data has been deposited to Dryad (https://doi.org/10.5061/dryad.sxksn0348). The dataset contains the Microcal Origin opj files of the electrical and optical recordings and quantitative analysis of the data. We are unable to make all raw electrical recording and imaging data publicly available as due to the large size of our raw dataset (>10TB). Interested researchers should contact the corresponding author to gain access to the raw data.
-
Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical neuronsDryad Digital Repository, doi:10.5061/dryad.sxksn0348.
Article and author information
Author details
Funding
Israel Science Foundation (1384/19)
- Ilya Fleidervish
Israel Science Foundation (1310/19)
- Daniel Gitler
National Institutes of Health (RF1 AG065628)
- Israel Sekler
National Institutes of Health (RF1 AG065628)
- Grace E Stutzmann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were approved by the Animal Care and Use Committee of Ben Gurion University of the Negev (protocol #IL-68-09-2019).
Copyright
© 2022, Stoler et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,796
- views
-
- 376
- downloads
-
- 18
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical
eLife 11:e74606.
https://doi.org/10.7554/eLife.74606
Further reading
-
- Neuroscience
Memory consolidation during sleep depends on the interregional coupling of slow waves, spindles, and sharp wave-ripples (SWRs), across the cortex, thalamus, and hippocampus. The reuniens nucleus of the thalamus, linking the medial prefrontal cortex (mPFC) and the hippocampus, may facilitate interregional coupling during sleep. To test this hypothesis, we used intracellular, extracellular unit and local field potential recordings in anesthetized and head restrained non-anesthetized cats as well as computational modelling. Electrical stimulation of the reuniens evoked both antidromic and orthodromic intracellular mPFC responses, consistent with bidirectional functional connectivity between mPFC, reuniens and hippocampus in anesthetized state. The major finding obtained from behaving animals is that at least during NREM sleep hippocampo-reuniens-mPFC form a functional loop. SWRs facilitate the triggering of thalamic spindles, which later reach neocortex. In return, transition to mPFC UP states increase the probability of hippocampal SWRs and later modulate spindle amplitude. During REM sleep hippocampal theta activity provides periodic locking of reuniens neuronal firing and strong crosscorrelation at LFP level, but the values of reuniens-mPFC crosscorrelation was relatively low and theta power at mPFC was low. The neural mass model of this network demonstrates that the strength of bidirectional hippocampo-thalamic connections determines the coupling of oscillations, suggesting a mechanistic link between synaptic weights and the propensity for interregional synchrony. Our results demonstrate the presence of functional connectivity in hippocampo-thalamo-cortical network, but the efficacy of this connectivity is modulated by behavioral state.
-
- Neuroscience
Studying infant minds with movies is a promising way to increase engagement relative to traditional tasks. However, the spatial specificity and functional significance of movie-evoked activity in infants remains unclear. Here, we investigated what movies can reveal about the organization of the infant visual system. We collected fMRI data from 15 awake infants and toddlers aged 5–23 months who attentively watched a movie. The activity evoked by the movie reflected the functional profile of visual areas. Namely, homotopic areas from the two hemispheres responded similarly to the movie, whereas distinct areas responded dissimilarly, especially across dorsal and ventral visual cortex. Moreover, visual maps that typically require time-intensive and complicated retinotopic mapping could be predicted, albeit imprecisely, from movie-evoked activity in both data-driven analyses (i.e. independent component analysis) at the individual level and by using functional alignment into a common low-dimensional embedding to generalize across participants. These results suggest that the infant visual system is already structured to process dynamic, naturalistic information and that fine-grained cortical organization can be discovered from movie data.
