Structural plasticity of synaptic connectivity in the adult central nervous system

Introduction - Overview: Neuroscience aims at understanding how we perceive, move, think, and remember using trillions of neurons. Every day our brain receives massive amounts of electrical and chemical signals that are processed through connected networks of neurons, which must be built with high specificity in order to produce meaningful and predictable information. Neurons transmit these signals to one another at specialized sites called synapses. These are excitatory or inhibitory, and accordingly increase or decrease neuronal responses. Thus, synapse development, maturation and dynamic is crucial in establishing proper functional neuronal circuits. In recent years it has become clear that synapses can be produced and dismantled even in the adult brain. As a consequence, dendritic spines and axonal boutons can appear and disappear throughout life. This neuronal remodeling is called “structural plasticity” and might be fundamental to learning, memory and cognition. In this introduction I describe some of the key components that are important to deal with structural plasticity of axon terminals in the adult. I will first start by explaining how synapses form during development, a process likely to also be relevant to how “mature synapses” might form in the adult brain. I will then report on what is known about axonal structural plasticity in the adult, and finally introduce the hippocampus as a model system to study structural plasticity. General Discussion - Overview: Recent neurobiological studies have begun to reveal the cognitive and neuronal coding mechanisms that underly episodic learning and memory (Vazdarjanova et al. 2004, Guzowski et al. 2001, Gabrieli et al. 1997 and Henke et al. 1997). The hippocampus has been shown to encode the sequences of places and events that compose episodic memories, and plays a critical role between the initial formation and their final repository elsewhere in the brain (Gabrieli et al. 1997 and Henke et al. 1997). However, we have only begun to conceptualize how information is encoded and preserved for long periods within the hippocampus. In fact, the exact contribution of each hippocampal cell type, which molecules are predominant and which kind of plasticity is crucial, is still poorly understood. Here I discuss new insights of the hippocampal granule cell organization that might be crucial to encode information that compose episodic learning and memory. In summary, we found: (1) that hippocampal mossy fibers exhibit structural plasticity at the level of the large mossy fiber terminals (LMTs); (2) that this remodeling respond to experience and age, (3) is regulated by spiking activity and mGluR2-sensitive transmitter release from LMTs (4) and can define subtypes of hippocampal granule cells that seem to belong to distinct microcircuits