A structural basis for memory storage in mammals

Abstract

AbstractÐIt is proposed that altered dendrite length and de novo formation of new dendrite branches in cholinoceptive cells are responsible for long-term memory storage, a process enabled by the degradation of microtubule-associated protein-2. These memories are encoded as modality-speci®c associable representations. Accordingly, associable representations are con®ned to cytoarchitectonic modules of the cerebral cortex, hippocampus, and amygdala. The proposed sequence of events leading to long-term storage in cholinoceptive dendrites begins with changes in neuronal activity, then in neurotrophin release, followed by enhanced acetylcholine release, muscarinic response, calcium in¯ux, degradation of microtubule-associated protein-2, and ®nally new dendrite structure. Hypothetically, each associable representation consists of altered dendrite segments from approximately 5000±15 000 cholinoceptive cells contained within one or a few module(s). Simultaneous restructuring during consolidation of long-term memory is hypothesized to result in a similar infrastructure among dendrite sets, facilitating co-activation of those dendrite sets by neurotransmitters such as acetylcholine, and conceivably enabling high energy interactions between those dendrites by phenomena such as quantum optical coherence. Based on the speci®c architecture proposed, it is estimated that the human telencephalon contains enough dendrites to encode 50 million associable representations in a lifetime, or put another way, to encode one new associable representation each minute. The implications that this proposal has regarding treatments for Alzheimer's disease are also discussed. #

Early changes in Huntington’s disease patient brains involve alterations in cytoskeletal and synaptic elements

“…Its function is also directly linked to its phosphorylation state, since phosphorylation of different domains leads to reduced tubulin binding (Brugg & Matus, 1991). MAP2 levels and conformation can be mediated by neurotransmitter systems (Halpain & Greengard, 1990;Diaz-Nido et al, 1993), whereby synaptic-mediated changes in the balance of kinases and phosphatases may alter MAP2 activity and, in turn, the microtubule network, allowing for synaptic plasticity (Avila et al, 1994;Woolf, 1998). Thus, a loss of MAP2 or an aberrant phosphorylation state may impair synaptic plasticity, as is noted in a murine model of HD (Usdin et al, 1999) and results in cognitive dysfunction.…”

Glutamatergic activity in the amygdala signals visceral input during taste memory formation

“…As noted, significant effects have been found when glutamatergic receptors were blocked before and after CTA acquisition in both the amygdala and IC (20 -22, 32, 33). The interaction of ACh and glutamate receptors is of special importance, considering that their activities may converge, as demonstrated by the study of the multiple signal-transduction pathways mediated by those receptors (34). Therefore, it has been demonstrated that one subunit of the NMDA receptor, the NR2B, undergoes phosphorylation by novel taste presentation or muscarinic activation (35).…”

Dendritic Encoding: An Alternative to Temporal Synaptic Coding of Conscious Experience

“…The conversion of temporal activity into the dendritic structure expands upon a data-based model that I proposed earlier whereby the microtubular structure is altered by reorganization of microtubule-associated protein-2 (MAP-2) in dendrite sets during the consolidation of memory (see Woolf, 1996Woolf, , 1997Woolf, , 1998. I have previously focused on the three-dimensional spatial organization of each altered dendrite set as a blueprint for conscious content (these dendrite sets are found throughout the neocortex, hippocampus, and amygdala).…”

“…For the sake of comparison, the dendritic encoding model (or the snapshot model) presented here also implicates attentional processes in consciousness. Neuromodulatory systems, such as the cholinergic basal forebrain neurons, meter attention at the same time they induce conscious awareness of stimuli (for reviews, see Woolf, 1996Woolf, , 1997Woolf, , 1998. Moreover, the muscarinic receptor for acetylcholine takes about 500 ms to completely respond.…”