The probability of neurotransmitter release: variability and feedback control at single synapses

Branco, Tiago; Staras, Kevin

doi:10.1038/nrn2634

Cited by 382 publications

(337 citation statements)

References 161 publications

Supporting

Mentioning

329

Contrasting

Order By: Relevance

“…Note that p 0 is not the same as p r , which is commonly used to refer to the probability of vesicle release for the entire synapse (6). In fact, p r is the probability that at least one vesicle is released when an action potential occurs, whereas p 0 is the probability of release per docked vesicle when an action potential occurs.…”

Section: Significancementioning

confidence: 99%

Improved signaling as a result of randomness in synaptic vesicle release

Zhang

Peskin

2015

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

View full text Add to dashboard Cite

The probabilistic nature of neurotransmitter release in synapses is believed to be one of the most significant sources of noise in the central nervous system. We show how p 0 , the probability of release per docked vesicle when an action potential arrives, affects the dynamics of the rate of vesicle release in response to changes in the rate of arrival of action potentials. Furthermore, we examine the theoretical capability of a synapse in the estimation of desired signals using information from the stochastic vesicle release events under the framework of optimal linear filter theory. We find that a small p 0 , such as 0.1, reduces the error in the reconstruction of the input, or in the reconstruction of the time derivative of the input, from the time series of vesicle release events. Our results imply that the probabilistic nature of synaptic vesicle release plays a direct functional role in synaptic transmission.synaptic transmission | stochastic vesicle release | release probability | optimal filter R andomness is present in almost all levels of all nervous systems, such as in ionic channels of individual neurons, in synapses between neurons, and in environmental stimuli. The probabilistic nature of the synaptic vesicle release process is believed to be one of the most significant sources of randomness. Stochastic vesicle release affects information transfer from a presynaptic neuron to a postsynaptic neuron, and hence may play not only an important role in synaptic plasticity (1, 2) but also a significant role in determining the functionality of certain synapses, a point we will argue in this article. The functional role of stochastic vesicle release in synaptic transmission is likely to be more significant in those synapses in the central nervous system, where the size of the readily releasable vesicle pool is usually smaller than those in the periphery.Synaptic vesicle release has only recently been studied in a probabilistic or information-theoretic manner (3-5). A systematic perspective on how stochastic vesicle release affects neural code processing at synapses is still lacking. On the experimental front, a comprehensive, quantitative knowledge about the nature of vesicle docking, priming, fusing, undocking, replenishing, and recycling is far from complete, and hence a biophysically detailed model of the entire vesicle release process is not yet possible.Despite current limited understanding of the synaptic vesicle release process, a probabilistic model that captures the essential elements of that process can still be built to study the effect of various sources of randomness on synaptic transmission. Rosenbaum et al. (3) recently constructed such a model to study how variability in vesicle dynamics affects information transfer from one neuron to another. They found that the depletion of docked vesicles at higher rates of arrival of action potentials makes the synapse act as a highpass filter from a signal processing point of view. Motivated by Rosenbaum et al.'s (3) model of the presynaptic vesicle r...

show abstract

Section: Significancementioning

confidence: 99%

Improved signaling as a result of randomness in synaptic vesicle release

Zhang

Peskin

2015

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

View full text Add to dashboard Cite

show abstract

“…Strikingly, no previous study had examined whether LAR-RPTPs themselves are involved in the presynaptic functions of mammalian neurons. To address these questions, we first monitored the paired-pulse ratio (PPR), a measure that is routinely used to identify changes in the neurotransmitter release probability (30). We first infected cultured hippocampal neurons with control lentiviruses (control) or coinfected them with lentiviruses expressing sh-LAR/sh-PTPσ and measured the PPR, which was calculated by delivering two stimuli 20 ms apart and then dividing the amplitude of the second excitatory postsynaptic current (EPSC 2 ) by the amplitude of the first EPSC (EPSC 1 ).…”

Section: The Hs-binding Sequence Of Ptpσ Is Essential For Excitatory mentioning

confidence: 99%

PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission

Pramanik

et al. 2015

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

View full text Add to dashboard Cite

Leukocyte common antigen-related receptor protein tyrosine phosphatases-comprising LAR, PTPδ, and PTPσ-are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTPσ. GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTPσ. PTPσ bound only to proteolytically cleaved GPC-4 and formed additional complex with leucine-rich repeat transmembrane protein 4 (LRRTM4) in rat brains. Moreover, single knockdown (KD) of PTPσ, but not LAR, in cultured neurons significantly reduced the synaptogenic activity of LRRTM4, a postsynaptic ligand of GPC-4, in heterologous synapse-formation assays. Finally, PTPσ KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTPσ, but not by a HS-binding-defective PTPσ mutant. Our results collectively suggest that presynaptic PTPσ, together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function.PTPσ | glypican | LRRTM4 | synaptic cell adhesion | heparan sulfate

show abstract

“…Such activation of signals occurs either at the presynaptic or postsynaptic level [6]. Blocking the normal functioning of the neurotransmitters might hamper the propagation of the active potential in a designated neural path [5,23].…”

Section: Major Neurotransmitters and Their Functionsmentioning

confidence: 99%

“…Moreover, research is being conducted to investigate such abnormalities for effective design and formulation of new therapeutics. A plethora of experimental evidences showed that the distribution and function of neurotransmitters are positively correlated with psychological events [5,6]. Molecular mechanisms associated with electrical gradients have been reported to alter the neurophysiology that impacts the psychometrics of the patient [7].…”

Section: Introductionmentioning

confidence: 99%

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

Choudhury¹,

Sahu²,

Ramanujam³

et al. 2018

Neuropsychiatry

View full text Add to dashboard Cite

Structural changes in different regions of the brain have become clinically relevant and regarded as the signature phenomenon for neurological diseases. Morphological changes in brain are also associated with neuronal and neurochemical alterations. Studies have showed that minute changes in neurochemical levels may have marked impact on the psychobehaviour of the subject. Several neurological disease profiles have been reported with such specific psychobehavioural expression. However, application of behavioural abnormalities as possible disease progress markers has not been considered and emphasised much. Reports suggested that-the subjects, who have already entered into the terminal stage of the disease, used to show cardinal behavioural signs for a specific disease profile. However, psychological expressions are comparatively early expressive. As most of the neurodegenerative disorders are unidirectional and progressive by nature, therapeutic intervention at the right time is essential for attaining the desired outcome. Moreover, early diagnosis can aid in managing the disease progression also. Psychobehavioural analysis could meet the expected outcome of disease diagnosis if implemented properly and timely. In the present review, we have amalgamated the reported behavioural anomalies with the supportive background from neurochemical basis. Further, we have concluded that behaviour centric studies could be a potential diagnostic tool for the early diagnosis of major neurological diseases such as Alzheimer disease, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), Bipolar disorder, Schizophrenia, Impulse control disorder (ICD) and Obsessive-compulsive disorder (OCD).

show abstract

The probability of neurotransmitter release: variability and feedback control at single synapses

Cited by 382 publications

References 161 publications

Improved signaling as a result of randomness in synaptic vesicle release

Improved signaling as a result of randomness in synaptic vesicle release

PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

Contact Info

Product

Resources

About