A review on the neurobiological basis of memory

Experimental data obtained using both invertebrates and laboratory rodents have provided evidences that memory is based on changes in synaptic strenght ultimately leading to morpho-functional alterations involving the number and the area of active synapses, in the case of long term memory. In invertebrates, very simple associative learning is accompanied by rather complex changes at synaptic level involving changes in signal transduction pathways and induction of gene expression. Similar mechanisms have been hypothesized and partially proven also in mammalians. In particular, in vertebrates hippocampal long term potentiation (LTP) has been thouroughly explored as a synaptic model of memory. The strong dependence of memory trace formation on signal transduction activation is particularly intriguing when examinig the behavior of aged animals. Within this context, it has been shown in various rat brain areas, including hippocampus, that aging is associated with a defective translocation of protein kinase C (PKC), a phosphorylating enzyme which may participate to LTP consolidation. This defect appears to be due to a reduction in specific membrane anchoring proteins refer-red to as receptor for activated C kinase (RACK). These observations, together with data showing a preserved number of neurons in hippocampus of aged animals even is presence of spatial learning deficits, complexively suggest that age-related memory impairment may rely on neurotransmitter and signal transduction changes, rather than on neurodegeneration and neuronal loss, redirecting the perspective of a putative pharmacological intervention from neuroprotection to specific molecular targets.