The theme of persistent synaptic changes and their causal role in memory is taken up by Tobias Bonhoeffer, who summarizes the evidence that dendritic spines, where excitatory synapses are located, represent the basic cellular unit for memory long-term memory is stored in a set of spines that are formed or modified during learning and these changes may persist throughout the animalвЂ™s life.Д«ased on the findings of activity-induced transcriptional activation and synapse-specific local translation of proteins, Kelsey Martin expands on the idea that the basic building block of memory is the synapse, where both pre- and postsynaptic elements together with associated glial processes form an integral unit with an individual identity and distinct вЂњneighborhoodвЂќ. Drawing on an elegant set of studies, Michele Pignatelli, TomГЎs Ryan, and Susumu Tonegawa illustrate how recently developed techniques to tag and manipulate neurons have begun to establish a causal link between neuronal activity, persistent synaptic changes, and an animalвЂ™s memory-associated behaviors. In this Forum, a group of experts on the cellular mechanisms of memory were invited to present their views on вЂњwhat is memoryвЂќ, including where and how memory engrams are stored, consolidated, and retrieved. Indeed, early development of neural circuits, whereby neural activity sculpts synaptic connectivity, depends on processes similar to that associated with LTP and LTD in the adult brain and could be considered as the imprinting of memory engrams generated by early experience. In addition, LTP and LTD could also lead to the formation of new and elimination of old synapses and thus changes in structural connectivity in the brain. There is now general consensus that persistent modification of the synaptic strength via LTP and LTD of pre-existing connections represents a primary mechanism for the formation of memory engrams.

The discovery of activity-induced long-term potentiation (LTP) and long-term depression (LTD) of central synapses in the 1970s and 80s further sparked the interest of a whole generation of neurobiologists in studying synaptic plasticity and its relationship to memory. In his monumental treatise The Organization of Behavior (1949), Donald Hebb made a bold attempt to link these two lines of inquiry by postulating that perceptual memory resides in specific вЂњcell assembliesвЂќ formed by the strengthening of interneuronal connections due to correlated activities during memory acquisition. Neurobiological studies of memory over the past century have progressed along two relatively independent lines of inquiry: the top-down approach examines the animalвЂ™s behaviors associated with memory acquisition, consolidation, and retrieval, as well as the brain regions underlying these processes, whereas the bottom-up approach explores the cellular and circuit mechanisms of memory encoding and storage by examining the patterns of neuronal firing and the efficacy of synaptic transmission.

Where is memory stored in the brain