Ralf Schneggenburger

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alpha-Synuclein (alpha-syn) is a presynaptic protein present at most nerve terminals, but its function remains largely unknown. The familial forms of Parkinson's disease associated with multiplications of the alpha-syn gene locus indicate that overabundanc ...

During fear learning, associations between a sensory cue (conditioned stimulus, CS) and an aversive stimulus (unconditioned stimulus, US) are formed in specific brain circuits. The lateral amygdala (LA) is involved in CS-US integration; however, US pathway ...

Ca2+-dependent transmitter release is the most important signaling mechanism for fast information transfer between neurons. Transmitter release takes places at highly specialized active zones with sub-micrometer dimension, which contain the molecular machi ...

Regulated fusion of small synaptic vesicles and the ensuing release of neurotransmitter at nerve terminals underlies chemical synaptic transmission between neurons. This process of exocytosis is initiated by an increase in the intracellular Ca2+ concentrat ...

Large excitatory synapses are found at specific points in the neuronal circuits of the auditory brainstem, to enable fast information transfer and the preservation of acoustic timing information. The extracellular cues and signaling mechanisms that lead to ...

Diacylglycerol (DAG) and phorbol esters strongly potentiate transmitter release at synapses by activating protein kinase C (PKC) and members of the Munc13 family of presynaptic vesicle priming proteins. This PKC/Munc13 pathway has emerged as a crucial regu ...

The two fundamental forms of short-term plasticity, short-term depression and facilitation, coexist at most synapses, but little is known about their interaction. Here, we studied the interplay between short-term depression and facilitation at calyx of Hel ...

Parvalbumin (PV)-expressing interneurons (PV-INs) mediate well-timed inhibition of cortical principal neurons, and plasticity of these interneurons is involved in map remodeling of primary sensory cortices during critical periods of development. To assess ...

The large glutamatergic calyx of Held synapse in the auditory brainstem has become a powerful model for studying transmitter release mechanisms, but the molecular bases of presynaptic function at this synapse are not well known. Here, we have used single-c ...

excitatory synapses with multiple active zones ensure reliable and fast information transfer at specific points in neuronal circuits. However, the mechanisms that determine synapse size in CNS circuits are largely unknown. Here we use the calyx of Held syn ...

Ca2+-evoked transmitter release shows a high dynamic range over spontaneous release. We investigated the role of the Ca2+ sensor protein, Synaptotagmin2 (Syt2), in both spontaneous and Ca2+-evoked release under direct control of presynaptic Ca2+, usin ...

Parvalbumin-expressing inhibitory neurons in the mammalian CNS are specialized for fast transmitter release at their output synapses. However, the Ca2+ sensor(s) used by identified inhibitory synapses, including the output synapses of parvalbumin-expressin ...

Safety learning allows the identification of non-threatening situations, a learning process instrumental for survival and psychic health. In contrast to fear learning, in which a sensory cue (conditioned stimulus, CS) is temporally linked to a mildly avers ...

During fear learning, defensive behaviors like freezing need to be finely balanced in the presence or absence of threat-predicting cues (conditioned stimulus, CS). Nevertheless, the circuits underlying such balancing are largely unknown. Here, we investiga ...

Ca2+-dependent transmitter release occurs in a fast and in a slow phase, but the differential roles of Ca2+ buffers and Ca2+ sensors in shaping release kinetics are still controversial. Replacing extracellular Ca2+ by Sr2+ causes decreased fast release but ...

Developmental refinement of synaptic transmission can occur via changes in several pre- and postsynaptic factors, but it has been unknown whether the intrinsic Ca2+ sensitivity of vesicle fusion in the nerve terminal can be regulated during development. Us ...

The amygdala is a brain area critical for the formation of fear memories. However, the nature of the teaching signal(s) that drive plasticity in the amygdala are still under debate. Here, we use optogenetic methods to investigate the contribution of ventra ...

Transmitter release at synapses is regulated by preceding neuronal activity, which can give rise to short-term enhancement of release like post-tetanic potentiation (PTP). Diacylglycerol (DAG) and Protein-kinase C (PKC) signaling in the nerve terminal have ...

The localization and density of voltage-gated Ca2+ channels at active zones are essential for the amount and kinetics of transmitter release at synapses. RIM proteins are scaffolding proteins at the active zone that bind to several other presynaptic protei ...

Various Synaptotagmin (Syt) isoform genes are found in mammals, but it is unknown whether Syts can function redundantly in a given nerve terminal, or whether isoforms can be switched during the development of a nerve terminal. Here, we investigated the pos ...

Ralf Schneggenburger

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Nigrostriatal overabundance of alpha-synuclein leads to decreased vesicle density and deficits in dopamine release that correlate with reduced motor activity

A posterior insula to lateral amygdala pathway transmits US-offset information with a limited role in fear learning

Ca2+ channels and transmitter release at the active zone

Exocytosis: Ca2+-Sensitivity

Role of BMP Signaling for the Formation of Auditory Brainstem Nuclei and Large Auditory Relay Synapses

Phorbol esters modulate spontaneous and Ca2+-evoked transmitter release via acting on both munc13 and protein kinase C

Interaction between Facilitation and Depression at a Large CNS Synapse Reveals Mechanisms of Short-Term Plasticity

LTP of inhibition at PV interneuron output synapses requires developmental BMP signaling

Developmental expression of Synaptotagmin isoforms in single calyx of Held-generating neurons

BMP signaling specifies the development of a large and fast CNS synapse

Synaptotagmin increases the dynamic range of synapses by driving Ca2+ - evoked release and by clamping a near-linear remaining Ca2+ sensor

Synaptotagmin2 (Syt2) Drives Fast Release Redundantly with Syt1 at the Output Synapses of Parvalbumin-Expressing Inhibitory Neurons

Auditory stimuli suppress contextual fear responses in safety learning independent of a possible safety meaning

A striatal circuit balances learned fear in the presence and absence of sensory cues

An Alien Divalent Ion Reveals a Major Role for Ca2+ Buffering in Controlling Slow Transmitter Release

Developmental regulation of the intracellular Ca2+ sensitivity of vesicle fusion and Ca2+-secretion coupling at the rat calyx of Held

A VTA to Basal Amygdala Dopamine Projection Contributes to Signal Salient Somatosensory Events during Fear Learning

Munc18-1 is a dynamically regulated PKC target during short-term enhancement of transmitter release

RIM1 and RIM2 redundantly determine Ca2+ channel density and readily releasable pool size at a large hindbrain synapse

A Synaptotagmin Isoform Switch during the Development of an Identified CNS Synapse