Multivesicular Release Differentiates the Reliability of Synaptic Transmission between the Visual Cortex and the Somatosensory Cortex

Huang, Caili; Bao, Jin; Sakaba, Takeshi

doi:10.1523/jneurosci.2381-10.2010

Cited by 27 publications

(33 citation statements)

References 69 publications

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“…Furthermore, agonist and/or antagonist can easily be applied to neurons in slice preparations. This allows one to study the effects of neuromodulators on the properties of synaptic transmission 32 or an in-depth characterization of a defined unitary synaptic connection using, for example, quantal analysis of synaptic release 16,17,38,39 . Finding of chemical and/or electrical (gap junction) synaptic connections is the most critical step of this protocol.…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological and Morphological Characterization of Neuronal Microcircuits in Acute Brain Slices Using Paired Patch-Clamp Recordings

Qi¹,

Radnikow²,

Feldmeyer

2015

JoVE

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The combination of patch clamp recordings from two (or more) synaptically coupled neurons (paired recordings) in acute brain slice preparations with simultaneous intracellular biocytin filling allows a correlated analysis of their structural and functional properties. With this method it is possible to identify and characterize both pre- and postsynaptic neurons by their morphology and electrophysiological response pattern. Paired recordings allow studying the connectivity patterns between these neurons as well as the properties of both chemical and electrical synaptic transmission. Here, we give a step-by-step description of the procedures required to obtain reliable paired recordings together with an optimal recovery of the neuron morphology. We will describe how pairs of neurons connected via chemical synapses or gap junctions are identified in brain slice preparations. We will outline how neurons are reconstructed to obtain their 3D morphology of the dendritic and axonal domain and how synaptic contacts are identified and localized. We will also discuss the caveats and limitations of the paired recording technique, in particular those associated with dendritic and axonal truncations during the preparation of brain slices because these strongly affect connectivity estimates. However, because of the versatility of the paired recording approach it will remain a valuable tool in characterizing different aspects of synaptic transmission at identified neuronal microcircuits in the brain.

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Section: Discussionmentioning

confidence: 99%

Electrophysiological and Morphological Characterization of Neuronal Microcircuits in Acute Brain Slices Using Paired Patch-Clamp Recordings

Qi¹,

Radnikow²,

Feldmeyer

2015

JoVE

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“…saline, n = 7 ± 3, n/m = 10/4; i.p. cocaine, n = 8 ± 1, n/m = 12/4; cocaine SA, n = 12 ± 5, n/m = 17/7) nor the quantal size ( receptors, the parabola of the variance-mean relationship bends (24). To test for receptor saturation, we perfused the NAc slice with 0.5 mM kynurenic acid in some experiments and repeated the stimulation to measure the variance-mean relationship with an apparent lower synaptic glutamate concentration (24,25).…”

Section: D-f)mentioning

confidence: 95%

“…cocaine, n = 8 ± 1, n/m = 12/4; cocaine SA, n = 12 ± 5, n/m = 17/7) nor the quantal size ( receptors, the parabola of the variance-mean relationship bends (24). To test for receptor saturation, we perfused the NAc slice with 0.5 mM kynurenic acid in some experiments and repeated the stimulation to measure the variance-mean relationship with an apparent lower synaptic glutamate concentration (24,25). The degrees of blockades of the first, second, and third stimuli before and after kynurenic acid were similar, all approximately 50%, suggesting that potential multivesicular release, if any, did not saturate the AMPARs under our conditions (Fig.…”

Section: D-f)mentioning

confidence: 95%

Selective presynaptic enhancement of the prefrontal cortex to nucleus accumbens pathway by cocaine

Suska

Lee

Huang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The nucleus accumbens (NAc) regulates motivated behavior by, in part, processing excitatory synaptic projections from several brain regions. Among these regions, the prefrontal cortex (PFC) and basolateral amygdala, convey executive control and affective states, respectively. Whereas glutamatergic synaptic transmission within the NAc has been recognized as a primary cellular target for cocaine and other drugs of abuse to induce addiction-related pathophysiological motivational states, the understanding has been thus far limited to drug-induced postsynaptic alterations. It remains elusive whether exposure to cocaine or other drugs of abuse influences presynaptic functions of these excitatory projections, and if so, in which projection pathways. Using optogenetic methods combined with biophysical assays, we demonstrate that the presynaptic release probability (Pr) of the PFC-to-NAc synapses was enhanced after short-term withdrawal (1 d) and long-term (45 d) withdrawal from either noncontingent (i.p. injection) or contingent (self-administration) exposure to cocaine. After long-term withdrawal of contingent drug exposure, the Pr was higher compared with i.p. injected rats. In contrast, within the basolateral amygdala afferents, presynaptic Pr was not significantly altered in any of these experimental conditions. Thus, cocaine-induced procedure-and pathway-specific presynaptic enhancement of excitatory synaptic transmission in the NAc. These results, together with previous findings of cocaine-induced postsynaptic enhancement, suggest an increased PFC-to-NAc shell glutamatergic synaptic transmission after withdrawal from exposure to cocaine. This presynaptic alteration may interact with other cocaine-induced cellular adaptations to shift the functional output of NAc neurons, contributing to the addictive emotional and motivational state.addiction | multiple probability fluctuation analysis | channelrhodopsin M edium spiny neurons (MSNs) within the nucleus accumbens (NAc) shell function to gate the emotional and motivational arousals for behavioral output (1). Glutamatergic synaptic input to the NAc provides the major driving force for MSNs and is targeted by drugs of abuse to produce adaptive changes (2). These drug-induced synaptic adaptations may substantially reshape the functional output of MSNs, leading to a preferential prioritization of addiction-related behavioral output. As such, elucidating cocaine-induced adaptive changes at NAc glutamatergic synapses has been a major task in understanding the neural basis underlying cocaine addiction. Whereas up-regulation of postsynaptic responsiveness of the NAc glutamatergic synapses after cocaine withdrawal are evident (3-5), it is not well understood whether the presynaptic input is also concurrently altered. Thus, the effect of cocaine on NAc glutamatergic synapses as a whole remains largely incomplete.A number of limbic and paralimbic regions project glutamatergic inputs to NAc shell neurons, each presumably carrying different aspects of emotional and motivational ...

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“…But MVR can also enable faithful transmission at intracortical synapses in layer 4 of the somatosensory cortex. Here, L4 neuron terminals display high P r and postsynaptic receptor saturation that reliably initiate action potentials, although MVR is less prevalent at L4 connections in the visual cortex [19]. It is possible that the differential expression of MVR represents distinct coding of information depending on content or valence.…”

Section: Functions Of Mvr Throughout the Brainmentioning

confidence: 99%

The ubiquitous nature of multivesicular release

Rudolph¹,

Tsai²,

Gersdorff³

et al. 2015

Trends in Neurosciences

133

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“Simplicity is prerequisite for reliability.”EW Dijkstra [1] Presynaptic action potentials trigger the fusion of vesicles to release neurotransmitter onto postsynaptic neurons. Each release site was originally thought to liberate at most one vesicle per action potential in a probabilistic fashion, rendering synaptic transmission unreliable. However, the simultaneous release of several vesicles, or multivesicular release (MVR), represents a simple mechanism to overcome the intrinsic unreliability of synaptic transmission. MVR was initially identified at specialized synapses but is now known to be common throughout the brain. MVR determines the temporal and spatial dispersion of transmitter, controls the extent of receptor activation, and contributes to adapting synaptic strength during plasticity and neuromodulation. MVR consequently represents a widespread mechanism that extends the dynamic range of synaptic processing.

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Multivesicular Release Differentiates the Reliability of Synaptic Transmission between the Visual Cortex and the Somatosensory Cortex

Cited by 27 publications

References 69 publications

Electrophysiological and Morphological Characterization of Neuronal Microcircuits in Acute Brain Slices Using Paired Patch-Clamp Recordings

Electrophysiological and Morphological Characterization of Neuronal Microcircuits in Acute Brain Slices Using Paired Patch-Clamp Recordings

Selective presynaptic enhancement of the prefrontal cortex to nucleus accumbens pathway by cocaine

The ubiquitous nature of multivesicular release

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