Abstract
Previous studies based on the ‘Quantal Model’ for synaptic transmission suggest that neurotransmitter release is mediated by a single release site at individual synaptic contacts in the neocortex. However, recent studies seem to contradict this hypothesis and indicate that multi-vesicular release (MVR) could better explain the synaptic response variability observed in vitro. In this study we present a novel method to estimate the number of release sites per synapse, also known as the size of the readily releasable pool (NRRP), from paired whole-cell recordings of connections between layer 5 thick tufted pyramidal cell (L5_TTPC) in the juvenile rat somatosensory cortex. Our approach extends the work of Loebel et al. (2009) by leveraging a recently published data-driven biophysical model of neocortical tissue. Using this approach, we estimated NRRP to be between two to three for synaptic connections between L5_TTPCs. To constrain NRRP values for other connections in the microcircuit, we developed and validated a generalization approach using published data on the coefficient of variation (CV) of the amplitudes of post-synaptic potentials (PSPs) from literature and comparing them against in silico experiments. Our study predicts that transmitter release at synaptic connections in the neocortex could be mediated by MVR and provides a data-driven approach to constrain the MVR model parameters in the microcircuit.
Highlights
Synaptic transmission is the basis for neuronal communication and information processing in the brain
To reproduce the synaptic release variability observed in vitro, we began by implementing univesicular release hypothesis (UVR) at all synaptic contacts in the neocortical microcircuit model
In order to further investigate the potential causes for this difference in response variability, we undertook wholecell recordings in vitro from 33 pairs of connected layer 5 thick tufted pyramidal cell (L5_TTPC) cells (Figure 1A, top) and computed the amplitude and the coefficient of variation (CV) of the amplitudes for each excitatory postsynaptic potential (EPSP)
Summary
Synaptic transmission is the basis for neuronal communication and information processing in the brain. Synaptic communication between neurons is mediated by neurotransmitters contained in presynaptic vesicles that are stochastically released from axonal boutons by incoming action potentials (APs) and diffuse across the synaptic cleft to bind receptors. Synaptic receptors are a class of ion channels which open as a result of transmitter binding, and the resulting transmembrane currents either depolarize or hyperpolarize the postsynaptic membrane, depending on the ion to which the channel is permeable (Mason et al, 1991; Südhof, 2000). Understanding the mechanisms behind vesicle release is crucial to unravel how information propagates between neuron types (Tsodyks and Markram, 1997). Disrupted vesicle release is implicated in pathologies such as Alzheimer’s disease or schizophrenia (Waites and Garner, 2011).
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