Presynaptic Mitochondria in Functionally Different Motor Neurons Exhibit Similar Affinities for Ca2+But Exert Little Influence as Ca2+Buffers at Nerve Firing RatesIn Situ

Chouhan, Amit K.; Zhang, Jinhui; Zinsmaier, Konrad E.; Macleod, Gregory T.

doi:10.1523/jneurosci.4701-09.2010

Cited by 72 publications

(118 citation statements)

References 90 publications

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“…Thus, we evaluated ER distribution in the iav 1 NMJs by expressing the ER marker, Lysozyme-KDEL::GFP (using UAS-Lyso::GFP-KDEL ; herein referred to as KDEL-GFP). Consistent with previous observations (Chouhan et al, 2010), we found that ER is distributed throughout the MN axons, and is also located within some, but not all, of the synaptic boutons (Figure 5H; arrows indicate ER in distal boutons). Despite an obvious decrease in the total number of boutons, presynaptic KDEL-GFP distribution is largely unchanged in iav 1 compared to controls (Figure 5I; arrows indicate ER in distal boutons).…”

Section: Resultssupporting

confidence: 93%

A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

Wong

Chen

Lin

et al. 2014

Neuron

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SUMMARY Presynaptic resting Ca2+ influences synaptic vesicle (SV) release probability. Here, we report that a TRPV channel, Inactive (Iav), maintains presynaptic resting [Ca2+] by promoting Ca2+ release from the endoplasmic reticulum in Drosophila motor neurons, and is required for both synapse development and neurotransmission. We find that Iav activates the Ca2+/calmodulin-dependent protein phosphatase, calcineurin, which is essential for presynaptic microtubule stabilization at the neuromuscular junction. Thus, loss of Iav induces destabilization of presynaptic microtubules resulting in diminished synaptic growth. Interestingly, expression of human TRPV1 in Iav-deficient motor neurons rescues these defects. We also show that the absence of Iav causes lower SV release probability and diminished synaptic transmission, whereas Iav overexpression elevates these synaptic parameters. Together, our findings indicate that Iav acts as a key regulator of synaptic development and function by influencing presynaptic resting [Ca2+].

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Section: Resultssupporting

confidence: 93%

A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

Wong

Chen

Lin

et al. 2014

Neuron

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“…Using a previously described method [39] we were able to determine the EFR for each of the two MNs (see also Figures S5A and S5B ). The EFR was significantly lower for MNSNb/d-Is than for MN6/7-Ib (Is: 7.8±0.7Hz; Ib: 20.7±0.8Hz; SEM, P<0.001; 2mM [Ca 2+ ] o ) ( Figure S5C ).…”

Section: Resultsmentioning

confidence: 99%

High-Probability Neurotransmitter Release Sites Represent an Energy-Efficient Design

Chouhan

Borycz

et al. 2016

Current Biology

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Nerve terminals contain multiple sites specialized for the release of neurotransmitters. Release usually occurs with low probability, a design thought to confer many advantages. High probability release sites are not uncommon but their advantages are not well understood. Here we test the hypothesis that high probability release sites represent an energy efficient design. We examined release site probabilities and energy efficiency at the terminals of two glutamatergic motor neurons synapsing on the same muscle fiber in Drosophila larvae. Through electrophysiological and ultrastructural measurements we calculated release site probabilities to differ considerably between terminals (0.33 vs. 0.11). We estimated the energy required to release and recycle glutamate from the same measurements. The energy required to remove calcium and sodium ions subsequent to nerve excitation was estimated through microfluorimetric and morphological measurements. We calculated energy efficiency as the number of glutamate molecules released per ATP molecule hydrolyzed, and high probability release site terminals were found to be more efficient (0.13 vs. 0.06). Our analytical model indicates that energy efficiency is optimal (~0.15) at high release site probabilities (~0.76). As limitations in energy supply constrain neural function, high probability release sites might ameliorate such constraints by demanding less energy. Energy efficiency can be viewed as one aspect of nerve terminal function, in balance with others, because high efficiency terminals depress significantly during episodic bursts of activity.

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“…It is assumed that mitochondria redistribute to provide a local source of ATP; and this is certainly a reasonable assumption. In addition mitochondria can either increase or decrease cyctoplasmic Ca 2+ signals by releasing Ca 2+ or by accumulating/buffering Ca 2+ (Demaurex et al, 2009; Kristian et al, 2007; Parnis et al, 2013; Chouhan et al, 2010). …”

Section: Coupling Of Glutamate Transport To Mitochondriamentioning

confidence: 99%

Astroglial glutamate transporters coordinate excitatory signaling and brain energetics

Robinson

Jackson

2016

Neurochemistry International

133

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In the mammalian brain, a family of sodium-dependent transporters maintains low extracellular glutamate and shapes excitatory signaling. The bulk of this activity is mediated by the astroglial glutamate transporters GLT-1 and GLAST (also called EAAT2 and EAAT1). In this review, we will discuss evidence that these transporters co-localize with, form physical (co-immunoprecipitable) interactions with, and functionally couple to various ‘energy-generating’ systems, including the Na+/K+-ATPase, the Na+/Ca2+ exchanger, glycogen metabolizing enzymes, glycolytic enzymes, and mitochondria/mitochondrial proteins. This functional coupling is bidirectional with many of these systems both being regulated by glutamate transport and providing the ‘fuel’ to support glutamate uptake. Given the importance of glutamate uptake to maintaining synaptic signaling and preventing excitotoxicity, it should not be surprising that some of these systems appear to ‘redundantly’ support the energetic costs of glutamate uptake. Although the glutamate-glutamine cycle contributes to recycling of neurotransmitter pools of glutamate, this is an over-simplification. The ramifications of co-compartmentalization of glutamate transporters with mitochondria for glutamate metabolism are discussed. Energy consumption in the brain accounts for ~20% of the basal metabolic rate and relies almost exclusively on glucose for the production of ATP. However, the brain does not possess substantial reserves of glucose or other fuels. To ensure adequate energetic supply, increases in neuronal activity are matched by increases in cerebral blood flow via a process known as ‘neurovascular coupling’. While the mechanisms for this coupling are not completely resolved, it is generally agreed that astrocytes, with processes that extend to synapses and endfeet that surround blood vessels, mediate at least some of the signal that causes vasodilation. Several studies have shown that either genetic deletion or pharmacologic inhibition of glutamate transport impairs neurovascular coupling. Together these studies strongly suggest that glutamate transport not only coordinates excitatory signaling, but also plays a pivotal role in regulating brain energetics.

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Presynaptic Mitochondria in Functionally Different Motor Neurons Exhibit Similar Affinities for Ca²⁺But Exert Little Influence as Ca²⁺Buffers at Nerve Firing RatesIn Situ

Abstract: Mitochondria accumulate within nerve terminals and support synaptic function, most notably through ATP production.

Cited by 72 publications

References 90 publications

A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

High-Probability Neurotransmitter Release Sites Represent an Energy-Efficient Design

Astroglial glutamate transporters coordinate excitatory signaling and brain energetics

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