Exo-endocytosis at mossy fiber terminals: Toward capacitance measurements in cells with arbitrary geometry

Kushmerick, Christopher; Gersdorff, Henrique von

doi:10.1073/pnas.1633427100

Cited by 7 publications

(10 citation statements)

References 30 publications

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“…Membrane capacitance measurements have been extremely useful to study single cell secretion and synaptic transmitter release (Neher and Marty, 1982), but they have been performed mostly from neuroendocrine cells and large nerve terminals with relatively simple morphologies and electrotonic structures (Kushmerick and von Gersdorff, 2003; Kawaguchi and Sakaba, 2015). However, there are several examples of successful measurements of ΔC m from cells with complex geometry and multiple electrical compartments (Hsu and Jackson, 1996; Mennerick et al 1997; Hallermann et al, 2003; Oltedal and Hartveit, 2010).…”

Section: Discussionmentioning

confidence: 99%

Synaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian Retina

Balakrishnan

Puthussery

Kim

et al. 2015

Neuron

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Summary Ribbon synapses convey sustained and phasic excitatory drive within retinal microcircuits. However, the properties of retinal inhibitory synapses are less well known. AII-amacrine cells are interneurons in the retina that exhibit large glycinergic synapses at their dendritic lobular appendages. Using membrane capacitance measurements we observe robust exocytosis elicited by the opening of L-type Ca2+ channels located on the lobular appendages. Two pools of synaptic vesicles were detected: a small, rapidly releasable pool and a larger and more slowly releasable pool. Depending on the stimulus, either paired-pulse depression or facilitation could be elicited. During early postnatal maturation, the coupling of the exocytosis Ca2+-sensor to Ca2+ channel becomes tighter. Light-evoked depolarizations of the AII-amacrine cell elicited exocytosis that was graded to light intensity. Our results suggest that AII-amacrine cell synapses are capable of providing both phasic and sustained inhibitory input to their postsynaptic partners without the benefit of synaptic ribbons.

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Section: Discussionmentioning

confidence: 99%

Synaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian Retina

Balakrishnan

Puthussery

Kim

et al. 2015

Neuron

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“…Cytoplasmic resistivity is in general difficult to measure accurately and estimates range from ϳ50 to ϳ500 ⍀cm (Hallermann et al 2003;Major et al 1994;Thurbon et al 1994;Trevelyan and Jack 2002;Ulrich et al 1994). The chosen value for cytoplasmic resistivity (R i ) is important, however, as it influences the overall degree of electrotonic compactness of a neuron (Spruston et al 1994).…”

Section: Effect Of Cytoplasmic Resistivity On Estimate Of Terminal Sizementioning

confidence: 99%

“…Our knowledge of the fundamental mechanisms of synaptic transmission is, to a large extent, based on information obtained from a relatively small number of experimental model systems with the neuromuscular junction being the classically studied system (Kushmerick and von Gersdorff 2003). During the last 20 yr, model systems for investigating synaptic transmission at the same level of mechanistic detail in the CNS have been developed.…”

Section: Introductionmentioning

confidence: 99%

Patch-Clamp Investigations and Compartmental Modeling of Rod Bipolar Axon Terminals in an In Vitro Thin-Slice Preparation of the Mammalian Retina

Oltedal

Mørkve²,

Veruki³

et al. 2007

Journal of Neurophysiology

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Oltedal L, Mørkve SH, Veruki ML, Hartveit E. Patch-clamp investigations and compartmental modeling of rod bipolar axon terminals in an in vitro thin-slice preparation of the mammalian retina. J Neurophysiol 97: [1171][1172][1173][1174][1175][1176][1177][1178][1179][1180][1181][1182][1183][1184][1185][1186][1187] 2007. First published December 13, 2006; doi:10.1152/jn.01010.2006. To extend the usefulness of rod bipolar cells for studies of chemical synaptic transmission, we have performed electrophysiological recordings from rod bipolar axon terminals in an in vitro slice preparation of the rat retina. Whole cell recordings from axon terminals and cell bodies were used to investigate the passive membrane properties of rod bipolar cells and analyzed with a two-compartment equivalent electrical circuit model developed by Mennerick et al. For both terminal-and soma-end recordings, capacitive current decays were well fitted by biexponential functions. Computer simulations of simplified models of rod bipolar cells demonstrated that estimates of the capacitance of the axon terminal compartment can depend critically on the recording location, with terminal-end recordings giving the best estimates. Computer simulations and whole cell recordings demonstrated that terminal-end recordings can yield more accurate estimates of the peak amplitude and kinetic properties of postsynaptic currents generated at the axon terminals due to increased electrotonic filtering of these currents when recorded at the soma. Finally, we present whole cell and outside-out patch recordings from axon terminals with responses evoked by GABA and glycine, spontaneous inhibitory postsynaptic currents, voltage-gated Ca 2ϩ currents, and depolarization-evoked reciprocal synaptic responses, verifying that the recorded axon terminals are involved in normal pre-and postsynaptic relationships. These results demonstrate that axon terminals of rod bipolar cells are directly accessible to whole cell and outside-out patch recordings, extending the usefulness of this preparation for detailed studies of pre-and postsynaptic mechanisms of synaptic transmission in the CNS.

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“…When standard capacitance techniques are extended from simple RC‐circuits and applied to morphological structures with arbitrary geometry, the accuracy of measurements designed to detect the increase of capacitance evoked by exocytosis cannot be calculated analytically. Instead, it is necessary to carefully validate any given method by compartmental modeling (Hallermann et al ; Kushmerick and von Gersdorff ). For AII amacrine cells, the goal is to quantify the capacitance increase evoked by exocytosis of glycine occurring at the synapses located at their lobular appendages.…”

Section: Discussionmentioning

confidence: 99%

“…When standard capacitance measurement techniques are applied to an unbranched, round cell using whole‐cell recording and sine wave voltage commands, the cell is represented by a simple, electrically equivalent RC‐circuit. Because neurons are branched structures with varying degrees of complex geometry, there has been considerable interest in the possibility of extending capacitance measurements from cells with simple and compact geometry to more general classes of neurons with complex branching (Kushmerick and von Gersdorff ; Kim and von Gersdorff ). This includes whole‐cell recordings from mossy fiber boutons in the hippocampus (Hallermann et al ), axon terminals of goldfish Mb1 bipolar cells (Heidelberger et al ; von Gersdorff and Matthews ) and rat rod bipolar cells (Oltedal and Hartveit ), axon terminals of the brainstem calyx of Held (Sun and Wu ; Wölfel and Schneggenburger ), and axon terminals of neurons in the posterior pituitary gland (Hsu and Jackson ).…”

Section: Introductionmentioning

confidence: 99%

Capacitance measurement of dendritic exocytosis in an electrically coupled inhibitory retinal interneuron: an experimental and computational study

2019

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Exocytotic release of neurotransmitter can be quantified by electrophysiological recording from postsynaptic neurons. Alternatively, fusion of synaptic vesicles with the cell membrane can be measured as increased capacitance by recording directly from a presynaptic neuron. The “Sine + DC” technique is based on recording from an unbranched cell, represented by an electrically equivalent RC‐circuit. It is challenging to extend such measurements to branching neurons where exocytosis occurs at a distance from a somatic recording electrode. The AII amacrine is an important inhibitory interneuron of the mammalian retina and there is evidence that exocytosis at presynaptic lobular dendrites increases the capacitance. Here, we combined electrophysiological recording and computer simulations with realistic compartmental models to explore capacitance measurements of rat AII amacrine cells. First, we verified the ability of the “Sine + DC” technique to detect depolarization‐evoked exocytosis in physiological recordings. Next, we used compartmental modeling to demonstrate that capacitance measurements can detect increased membrane surface area at lobular dendrites. However, the accuracy declines for lobular dendrites located further from the soma due to frequency‐dependent signal attenuation. For sine wave frequencies ≥1 kHz, the magnitude of the total releasable pool of synaptic vesicles will be significantly underestimated. Reducing the sine wave frequency increases overall accuracy, but when the frequency is sufficiently low that exocytosis can be detected with high accuracy from all lobular dendrites (~100 Hz), strong electrical coupling between AII amacrines compromises the measurements. These results need to be taken into account in studies with capacitance measurements from these and other electrically coupled neurons.

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Exo-endocytosis at mossy fiber terminals: Toward capacitance measurements in cells with arbitrary geometry

Cited by 7 publications

References 30 publications

Synaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian Retina

Synaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian Retina

Patch-Clamp Investigations and Compartmental Modeling of Rod Bipolar Axon Terminals in an In Vitro Thin-Slice Preparation of the Mammalian Retina

Capacitance measurement of dendritic exocytosis in an electrically coupled inhibitory retinal interneuron: an experimental and computational study

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