Brain and memory: Old arguments and new perspectives.

brain research 1621 (2015) 1–4 Available online at www.sciencedirect.com www.elsevier.com/locate/brainres Editorial Brain and memory: Old arguments and new perspectives The question of how the brain stores, organizes, and retrieves memories is one of the longest running and intensely argued issues in the biological sciences. It is easy to ﬁnd reasons why this should be so. Casual introspection, more than a century of research and debates tells us that an understanding of memory is an essential, early step towards a theory of mental life and the phenomenon is profoundly mysterious, a feature bound to attract scholars. Memories form quickly (albeit with a still poorly understood stabilization period), can be remark- ably persistent, and the brain possesses an almost unbelie- vable storage capacity. Moreover, all lines of evidence point to the conclusion that memories are scattered throughout the brain and yet are (1) organized into computationally efﬁcient structures, and along several dimensions, and (2) rapidly recalled even across different sensory modalities. Finding a unifying explanation for these qualities makes for a fascinat- ing and challenging problem; this challenge, combined with the central role played by memory in all human experience, likely explains the continuing intensity of research in the ﬁeld. But the very nature of the properties of memories suggests that consensus deﬁnitions, conclusive experiments and con- vincing arguments will be hard to come by. The past 50 years of work has amply conﬁrmed this prediction. Seen in this light, the many and sometimes acrimonious arguments associated with memory research were probably inevitable. However, scientiﬁc controversies often have useful outcomes and the question arises as to whether this has been the case for memory research. The contributions to this Special Issue were intended to address this question. They are organized into sections on a spectrum beginning with studies related to encoding mechanisms and ending with psychiatric disorders. The papers in each group deal with old arguments, including those related to the brain changes that encode new memory, how these are affected by events in the body, where storage occurs, and how all of these processes are integrated into higher cognitive functions. They describe the latest develop- ments along with intriguing new perspectives. the coining of the term ‘synapse’ by Sherrington in 1897. The French psychologist, Theodule Ribot wrote in 1882 that ‘the physiological conditions of memory’ must include ‘an asso- ciation, a speciﬁc connection established between a given number of elements’. Later, he speculates that the associa- tion will ‘… by repetition, become as stable as the primitive anatomical connections’. Ribot was worried that permanent changes in the state of a neuron (‘permanently polarized’ in his terminology) would limit storage capacity, an issue that continues to encourage the assumption that storage occurs at connections rather than through whole cell modiﬁcations. Today, of course, we have much stronger, experimentally grounded reasons for accepting the hypothesis that synaptic modiﬁcations are the substrate for encoding. The discovery of the long-term potentiation (LTP) phenomenon by Bliss and Lomo (1973) demonstrated that synapses possess character- istics required for a storage element; rapid changes in strength, triggered by physiologically reasonable stimulation patterns, and extreme persistence. Those ﬁrst experiments also provided evidence that the changes were synapse speciﬁc, a point that was ﬁrmly established by studies using the then newly introduced hippocampal slice preparation. Later came results showing that drugs that block LTP cause amnesia (Morris et al., 1986) and clear demonstrations that the potentiation effect occurs at predicted synapses during learning (Roman et al., 1987). Ribot would have understood and been delighted by these discoveries. But intense controversies soon erupted. The ﬁrst, and perhaps most severe of these, concerned the locus of the synaptic modiﬁcation underlying LTP was due to an increase in transmitter release or an enhanced post-synaptic response. This debate has subsided in part because the post- but not the pre-synaptic camp succeeded in identifying detailed mechanisms supporting their argument. But the signaling cascades leading to post-synaptic LTP have them- selves become the subjects of considerable argument. Papers in Section A of this Special Issue review the canonical ideas and show that these are either questionable or far from complete. The next part of the section deals with a historical, Synapses and memory and very contemporary, dispute about the reasons why LTP and memory endures for such remarkable periods. Three The idea that connections between neurons are encoding and storage sites for memories is very old, and probably predates very different ideas have been advanced, including new synapse formation, self-regenerating chemical systems that