Topic: CA3-CA1 synapses

CA3-CA1 synapses in the hippocampus are the initial locus of episodic memory. The action of acetylcholine alters cellular excitability, modifies neuronal networks, and triggers secondary signaling that directly affects long-term plasticity (LTP) (the cellular underpinning of memory). It is therefore considered a critical regulator of learning and memory in the brain. Its action via M4 metabotropic receptors in the presynaptic terminal of the CA3 neurons and M1 metabotropic receptors in the postsynaptic spines of CA1 neurons produce rich dynamics across multiple timescales. We developed a model

Introduction: Neurotrypsin (NT) is a neuronal trypsin-like serine protease whose mutations cause severe mental retardation in humans. NT is activated in vitro by Hebbian-like conjunction of pre- and postsynaptic activities, which promote the formation of dendritic filopodia via proteolytic cleavage of the proteoglycan agrin. Aims: 1) to examine the functional importance of NT for synaptic plasticity, learning, and extinction of memory in juvenile and matured mice, and 2) to evaluate the therapeutic potential of an NT-generated fragment of agrin, agrin-22. Methods: 1-month-old “Juvenile” NT−/−