Consciousness pyramidal cells

Muscarinic receptor activation of cortical pyramidal cells occurs with a latency of around 250 msec (Taylor 8c Brown, 1999). There is also an approximate 500 msec time lag between the occurrence of a stimulus and consciousness of that stimulus (Libet et ah, 1991). Hence the typical delay associated with muscarinic action (and that of other metabotropic receptors) coincides with the time lag for stimuli reaching consciousness. Thus, cholinergic affer-ents to the cerebral cortex may contribute to 40 Hz activity, as well as to larger envelopes of activity (or inactivity) lasting 250-500 msec. 

Cortical and hippocampal pyramidal cells are noteworthy in at least three ways (1) they are preferentially, but not exclusively, innervated by cholinergic terminals (2) they are implicated as a potential site of consciousness and (3) they are enriched with cytoskeletal proteins, some of which undergo hyperphosphorylation in Alzheimer s disease. A novel signal transduction mode may exist within the large pyramidal cells of the cerebral cortex and hippocampus. 

Multiple premises exist for the large layer 5 pyramidal cells being critical to consciousness. Crick and Koch (1992) have hypothesized that the large layer 5 pyramidal cells are correlated most closely with consciousness because they fire in bursts and send information completely out of the cortex. HamerofF and Penrose (1996) have suggested the cortical microtubule, tuned by the MAP-2 protein, as the site of conscious computation in the brain. This implicates the large layer 5 pyramidal cells because they are enriched with MAP-2 protein (Woolf, 1993). 

Moreover, all cells are not equally targeted in Alzheimer s disease, a disease that has discernable effects on consciousness (Perry et al., 1999). Large pyramidal cells of the frontal and temporal cortex, as well as the large pyramidal cells in CAl of hippocampus and subiculum, are the most susceptible to develop neurofibrillary tangles, to become dysfunctional and ultimately to die (Mann, 1996). It is the accumulation of abnormally hyperphosphorylated tau that disrupts the microtubular system of pyramidal cells in cortex and hippocampus both in experimental animal models and in Alzheimer s disease brain (Gong et al., 2000). 

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