Becoming memories: consolidation

The hypothesis that new memories consolidate slowly over time was proposed some 100 years ago, and continues to guide memory research. In modern consolidation theory, it is assumed that new memories are initially “labile” and sensitive to disruption before undergoing a series of processes (e.g., glutamate release, protein synthesis, neural growth and rearrangement) that render the memory representations progressively more stable. These processes are generally referred to as “consolidation”.

The famous researcher of biochemical mechanisms of learning and memory Steven P.R. Rose has found the young chick as a powerful model system in which to study the biochemical and morphological processes underlying memory formation. In the reviews (Rose, 2000, 2005) he argues that chicks, being precocial birds, need to actively explore and learn about their environment from the moment they hatch; they learn very rapidly to distinguish edible from inedible or distasteful food, and to navigate complex routes. Training paradigms that exploit these species-specific tasks work with the grain of the animal’s biology, and because such learning is a significant event in the young chick’s life the experiences involved may be expected to result in readily measurable brain changes. At the same time, when working with chicks researchers have applied one of the few universal findings in studies of biochemical processes in memory formation, namely that long - term memory is protein synthesis dependent (Davies and Squire, 1984).

The learning protocol that has been used in the Rose’s lab does not demand excellent cognitive skills from day old birds. Nevertheless, their stable and well working memory is amazing. Chicks are held in pairs in small pens, pre-trained by being offered a small dry white bead, and those that peck trained with a larger chrome or coloured bead coated with the distasteful substance. Chicks that peck such a bead show a disgust reaction (backing away, shaking their heads and wiping their beaks) and will avoid a similar but dry bead for at least 48 hours. However, they continue to discriminate, as shown by pecking at control beads of other colours.

This method enabled experimenters to identify a biochemical cascade associated with memory consolidation in the minutes to hours following training. Thus a change in some biochemical marker at a specific post-training time, occurring in trained compared with control chicks, might imply its direct engagement in memory expression at that time. Alternatively it could indicate the mobilisation of that marker as a part of a sequence leading to the synthesis of a molecule, or cellular reorganisation, required for the expression of memory. A similar argument applies to the timing of the onset of amnesia following intracerebral drug injection.

The detailed description of biochemical mechanisms of learning is available in books and papers generated by this research group and other specialists in this field (see, for example, Goelet et al., 1986; McGaugh, 1989, Damasio, 1994; Anokhin et al., 1991; Tiunova et al., 1998; Freeman, 1999; Rose and Stewart, 1999). The training experience generates a sequence of rapid synaptic transients which provide a temporary ‘hold’ for the memory - the phases categorised as short and intermediate term memory. As well as forming the brain substrate of the remembered avoidance over this period, these transients serve two other functions. They initiate the sequence of pre- and post-synaptic intracellular processes which will in due course result in the lasting 'synaptic' changes presumed to underlie long term memory, and they also serve to “tag” relevant active synapses, so as to indicate those synapses later to be more lastingly modified.

The study of long-term memory has revealed the extensive dialog between the synapse and the nucleus, and the nucleus and the synapse. In the long-term process the response of a synapse is not determined simply by its own history of activity (as in short-term plasticity), but also by the history of transcriptional activation in the nucleus.

Investigations and manipulations with the sequence of biochemical events occurring in the chick’s brain that faces a problem of avoidance of irrelevant food items allowed constructing an integrative picture of memory consolidation beyond cellular theories of memory formation, which is heavily based on Hebbian models. Memory appears to be not just a pre/post synaptic event; rather, whether any particular experience is learned or not depends on a much wider array of neural and peripheral factors, humoral and perhaps also immunological. Furthermore the magnitude and diverse locations in space and time of the changes that have been found following training on such a simple learning task demands that researchers re-conceptualise their model of memory storage, moving from a fixed and linear view of memory formation to a more dynamic concept, involving large ensembles of cells differentially distributed in space and time (Rose, 1993).

10. BEHAVIOURAL MECHANISMS OF EXPERIENCE OF TIME

When my dachshund calved, I decided to wire the new-born five puppies with common wonderful memories, just for fun. When they grew up enough for having food above their mother’s milk, I snapped my tongue in a specific manner every time the puppies were fed from their common bowl. Now I have a secrete password to enter a mind of each of them. Becoming adult and serious hunting dogs, they readily leave their owners to rush for my signal with infantile and pleased smile on their faces. Thus I have shaped five “Proustian” dogs who probably will keep these memories up to their old age. Everyone who somehow deals with animals has a collection of such anecdotes but we need strong experimental evidences of how learned skills become memories in order to judge about animals’ ability to navigate past and future in their life.