Biology Reference
In-Depth Information
modifications remains central in our current understanding of activity-dependent
development, learning, memory and brain damage (Chen and Tonegawa, 1997).
In 1973 it was discovered that brief tetanic stimulation produced a long lasting form of
synaptic plasticity, long-term potentiation (LTP) that can last for hours or days in the
mammalian hippocampus (Bliss and Lømo 1973). Just before that the involvement of the
hippocampal formation in memory was established by clinical data indicating that lesions of
this structure in humans produce anterograde amnesia (Milner 1966).
Throughout development and in adult life, the brain responds to experience by adjusting
the strength of communication at individual synapses and by changing the physical pattern of
synaptic connections between neurons. In this way, information can be stored by the nervous
system in the form of altered structure and chemistry of synapses and/or by the formation of
new synapses and the elimination of old ones. Neuronal plasticity is associated with critical
physiological processes in the developing and adult brain.
Activity-dependent remodeling of synaptic efficacy and neuronal connectivity is a
remarkable property of synaptic transmission and characteristic of plastic events in the
nervous system. Neuronal plasticity involves, in part, changes in cell morphology. These
changes have been observed as a consequence of a variety of experimental manipulations,
including associative learning (Black et al., 1990; Federmeier et al., 1994; Kleim et al., 1994,
1997), environmental rearing conditions (Turner and Greenough, 1985; Volkmar and
Greenough 1972), and increased synaptic "use" induced by direct electrical stimulation
(Wojtowicz et al., 1989; Geinisman, 1993; Buchs and Muller 1996;), as well as in relation to
the processes of normal development and aging (De Groot and Bierman 1983; Dyson and
Jones 1984; Harris et al., 1992). Structural characteristics identified as "plastic," or
susceptible to environmental and experiential influence, include size and shape of the
postsynaptic spine head, length of the postsynaptic spine neck, length and thickness of the
postsynaptic density (PSD), and changes in the number of presynaptic vesicles and
presynaptic active zones (Liaw et al., 1999).
It has been demonstrated that synapses are constantly being formed, eliminated and/or
reshaped. There is evidence that LTP of synaptic efficacy induces synaptic spine changes in
the hippocampus (Engert and Bonhoeffer, 1999; Toni et al., 1999). It was also shown that
synaptic structures undergo a conformational change after a treatment to induce olfactory
memory formation in mice (Matsuoka et al., 1997).
Adaptive reorganization of neuronal connectivity, which allows the acquisition of new
information, both during development and in the mature brain, is thus based upon the
strengthening of existing, synapses, the formation of new synapses and the destabilization of
previously established synaptic contacts. With the increasing need during evolution to
organize brain structures of increasing complexity, these processes of dynamic stabilization
and destabilization might become more and more important. At the same time, however, the
delicate balance between stabilization and destabilization might also provide the basis for an
increasing rate of failure. The effects of plasticity can, therefore, lead to either positive or
negative changes. Thus, one can envisage of a spectrum of types of neuronal modifications
that lead, at one end, to beneficial modifications as they may occur in learning and, at the
other end, to detrimental effects as neurodegeneration and cell death (Caroni, 1998;
McEachern and Shaw, 1999; Mattson and Furukawa, 1998).
An interesting finding of recent years is that synapses are extremely dynamic structures
that may change not only their functioning with activity but also their morphology. The
