Abstract
Understanding the molecular and cellular changes that underlie memory, the engram, requires the identification, isolation and manipulation of the neurons involved. This presents a major difficulty for complex forms of memory, for example hippocampus-dependent declarative memory, where the participating neurons are likely to be sparse, anatomically distributed and unique to each individual brain and learning event. In this paper, I discuss several new approaches to this problem. In vivo calcium imaging techniques provide a means of assessing the activity patterns of large numbers of neurons over long periods of time with precise anatomical identification. This provides important insight into how the brain represents complex information and how this is altered with learning. The development of techniques for the genetic modification of neural ensembles based on their natural, sensory-evoked, activity along with optogenetics allows direct tests of the coding function of these ensembles. These approaches provide a new methodological framework in which to examine the mechanisms of complex forms of learning at the level of the neurons involved in a specific memory.
Highlights
It has been known for over 60 years that medial temporal lobe (MTL) structures are necessary for declarative or explicit forms of memory [1]
To return to the declarative memory example discussed above, suppose that we found a set of neurons that responded to photos of your mother, and we demonstrated that we could artificially stimulate that specific set of neurons and the thought or perception of your mother popped into your head
How consistent is the pattern of brain activity in response to two identical sensory inputs or two different memory recall events? What is noise and what is signal in the pattern of neural activity that is observed? Certainly the brain’s ability to consistently recognize and learn about elements in the environment implies some coherent signal in the neural activity patterns induced by the same sensory stimulation, but the models and approaches to understanding this information will differ depending on whether the signal is a dominant or a minor component of the sensory-evoked activity
Summary
It has been known for over 60 years that medial temporal lobe (MTL) structures are necessary for declarative or explicit forms of memory [1]. While each of the two neural representations in this example have themselves been moulded by previous learning, we do not know the sites of plasticity that produced them, and so should not formally consider them engrams While these complex representations have been linked in a new declarative memory, the responsive neurons that we record are not necessarily the site of the plasticity that underlies this association. I suggest four requirements for the identification of a declarative memory engram, which parallel a set of criteria outlined by Martin et al [6] for testing the hypothesis that NMDA-dependent long-term potentiation (LTP) is a cellular mechanism for learning They are: (i) identify a learninginduced molecular and corresponding functional cellular change in a specific subset of neurons.
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