Biology Reference
In-Depth Information
changes in synaptic strength have been termed long-term potentiation (LTP) (Kuba and
Kumamoto, 1990; Patterson et al., 1996; Kovalchuk et al., 2002) and long-term depression
(LTD) (Bramham and Srebro, 1987; Ito, 1989; Ikegaya et al., 2002). In the hippocampus,
LTD can be produced when a low-frequency train of stimulus is negatively correlated in time
with a high-frequency conditioning input (Stanton and Sejnowski, 1989). The two classic
forms of long-term synaptic plasticity, LTP and LTD, are widely expressed at excitatory
synapses throughout the brain, possibly at every excitatory synapse in the mammalian brain,
and have been widely studied in several neural systems. In the brain, most synapses that
express LTP can also exhibit different forms of LTD and it is not clear that LTP and LTD are
not a unitary phenomena. LTD is considered to be a normal break mechanism preventing
saturation of LTP. It is now clear that there are different forms of LTP and LTD and they vary
depending on the synapses and circuits in which they operate (Kauer and Malenka, 2007).
Therefore, when studying synaptic plasticity, it is essential to define the types of LTP and
LTD that can occur at any specific synapses (Malenka and Bear, 2004).
LTP in the hippocampus is only one of several different forms of long-term synaptic
plasticity that exist in specific circuits in the mammalian brain. The prototypic form of
synaptic plasticity is LTP involving glutamate and its N-tethyl-D-aspartate receptors
(NMDAR) as well as its aamino-3-hydroxy-5-methyl-isoxazole propionic acid-glutamate
receptors (AMPAR). Several forms of LTP, which are dependent on NMDAR, induce and
increase the number of AMPAR, also expressed in the same synaptic terminal on the
postsynaptic neuron (Dozmorov et al., 2006; Lu et al., 2001). As a consequence, after the
induction of LTP there is also an increase in the ratio of AMPAR/NMDAR in the synaptic
terminal being activated. The consequence is an increased synaptic strength between the
active presynaptic and postsynaptic neurons, which become more sensitive to posterior
glutamate release.
There are other structural changes as a consequence of synaptic plasticity. One of the first
described was an increase in the number of synaptic spines and a decrease in spines' length,
also contributing to the potentiation of synaptic contacts (Hosokawa et al., 1995; Geinisman,
2000).
BDNF is a neurotrophic factor known to promote different forms of excitatory synaptic
plasticity, such as early- and late-phase long-term potentiation (LTP) in the Ca1 regions of the
hippocampus (Poo et al., 2001). BDNF also blocks LTD and facilitates LTP induction (Poo et
al., 2001) as well as induces neuroplastic changes in neurons promoting dendritic spine
formation and sprouting (Bramham and Messaoudi, 2005), changes that underlies normal
learning and memory processes. BDNF is synthesized and stored in glutamatergic neurons
and can be released in an activity-dependent manner from dendrites and axon
terminals
(Lessmann et al., 2003). BDNF is also a key element in the survival and differentiation of the
dopaminergic system (Thoenen, 1995) and its specific receptor TrkB is expressed in all
mesencephalic dopaminergic neurons (Numan and Seroogy, 1999), and in brain regions such
as the striatum (Yurek et al., 1996), the prefrontal cortex (Bland et al., 2005); and the
amygdala (Gordon et al., 2003). All these regions are involved in drug-induced neuronal
responses. Experimental evidence supports the existence of a cross-talk between the BDNF
intracellular signaling mechanisms and those of the glutamate and dopamine transmission,
possibly through protein kinases (PKA) and Ca2+. It has been reported that chronic cocaine
treatment results in a sustained increase in ERK activity via glutamate-dependent mechanisms
(Berhow et al., 1996) (see figure 1).
