Fully-primed slowly-recovering vesicles mediate presynaptic LTP at neocortical neurons.

Pre- and postsynaptic forms of long-term potentiation (LTP) are candidate synaptic mechanisms underlying learning and memory. At layer 5 pyramidal neurons, LTP increases the initial synaptic strength but also short-term depression during high-frequency transmission. This classical form of presynaptic LTP has been referred to as redistribution of synaptic efficacy.

Ca2.2 Channels Sustain Vesicle Recruitment at a Mature Glutamatergic Synapse.

The composition of voltage-gated Ca channel (Ca) subtypes that gate action potential (AP)-evoked release changes during the development of mammalian CNS synapses. Ca2.2 and Ca2.

The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release.

Humans carrying the CORD7 (cone-rod dystrophy 7) mutation possess increased verbal IQ and working memory. This autosomal dominant syndrome is caused by the single-amino acid R844H exchange (human numbering) located in the 310 helix of the C2A domain of RIMS1/RIM1 (Rab3-interacting molecule 1). RIM is an evolutionarily conserved multi-domain protein and essential component of presynaptic active zones, which is centrally involved in fast, Ca2+-triggered neurotransmitter release.

Developmental Increase of Neocortical Presynaptic Efficacy Maturation of Vesicle Replenishment.

The efficacy of neocortical synapses to transmit during bursts of action potentials (APs) increases during development but the underlying mechanisms are largely unclear. We investigated synaptic efficacy at synapses between layer 5 pyramidal neurons (L5PNs) during development, using paired recordings, presynaptic two-photon Ca imaging, and numerical simulations. Our data confirm a developmental increase in paired-pulse ratios (PPRs).

Neocortical High Probability Release Sites Are Formed by Distinct Ca Channel-to-Release Sensor Topographies during Development.

Coupling distances between Ca channels and release sensors regulate vesicular release probability (p). Tight coupling is thought to provide a framework for high p and loose coupling for high plasticity at low p. At synapses investigated during development, coupling distances decrease, thereby increasing p and transmission fidelity.

Synaptotagmin Ca Sensors and Their Spatial Coupling to Presynaptic Ca Channels in Central Cortical Synapses.

Ca concentrations drop rapidly over a distance of a few tens of nanometers from an open voltage-gated Ca channel (Ca), thereby, generating a spatially steep and temporally short-lived Ca gradient that triggers exocytosis of a neurotransmitter filled synaptic vesicle. These non-steady state conditions make the Ca-binding kinetics of the Ca sensors for release and their spatial coupling to the Cas important parameters of synaptic efficacy. In the mammalian central nervous system, the main release sensors linking action potential mediated Ca influx to synchronous release are Synaptotagmin (Syt) 1 and 2.

Munc13-3 Is Required for the Developmental Localization of Ca Channels to Active Zones and the Nanopositioning of Ca2.1 Near Release Sensors.

Spatial relationships between Ca channels and release sensors at active zones (AZs) are a major determinant of synaptic fidelity. They are regulated developmentally, but the underlying molecular mechanisms are largely unclear. Here, we show that Munc13-3 regulates the density of Ca2.

Developmental tightening of cerebellar cortical synaptic influx-release coupling.

Tight coupling between Ca(2+) channels and the sensor for vesicular transmitter release at the presynaptic active zone (AZ) is crucial for high-fidelity synaptic transmission. It has been hypothesized that a switch from a loosely coupled to a tightly coupled transmission mode is a common step in the maturation of CNS synapses. However, this hypothesis has never been tested at cortical synapses.

Paired-pulse facilitation at recurrent Purkinje neuron synapses is independent of calbindin and parvalbumin during high-frequency activation.

Paired-pulse facilitation (PPF) is a dynamic enhancement of transmitter release considered crucial in CNS information processing. The mechanisms of PPF remain controversial and may differ between synapses. Endogenous Ca(2+) buffers such as parvalbumin (PV) and calbindin-D28k (CB) are regarded as important modulators of PPF, with PV acting as an anti-facilitating buffer while saturation of CB can promote PPF.

Deletion of the cell adhesion adaptor protein vinculin disturbs the localization of GFAP in Bergmann glial cells.

Astrocytes operate in close spatial relationship to other cells including neurons. Structural interaction is controlled by a dynamic interplay between actin-based cell motility and contact formation via cell-cell and cell-extracellular matrix adhesions. A central player in the control of cell adhesion is the cytoskeletal adaptor protein Vinculin.

Nanodomain coupling at an excitatory cortical synapse.

The coupling distance between presynaptic Ca(2+) influx and the sensor for vesicular transmitter release determines speed and reliability of synaptic transmission. Nanodomain coupling (<100 nm) favors fidelity and is employed by synapses specialized for escape reflexes and by inhibitory synapses involved in synchronizing fast network oscillations. Cortical glutamatergic synapses seem to forgo the benefits of tight coupling, yet quantitative detail is lacking.