Biology Reference
In-Depth Information
Schaffer collateral pathway and also to other levels of CA3. The CA1 pyramidal cells give
rise to projections that terminate in the subiculum, which feeds back to the deep layers of the
entorhinal cortex (layers III, IV, V), thus resulting in an entorhinal-hippocampal-entorhinal
loop. The subiculum has a number of other outputs, sending projections also to the frontal
cortex and the presubiculum. Presubiculum projections also connect back to the entorhinal
cortex (layers III, IV, V, IV). Other minor ipsilateral pathways, as well as callosal pathways
that provide communication with the contralateral hemisphere, also exist.
Long-term potentiation (LTP)
LTP is believed to contribute to synaptic plasticity in living animals, providing a basis for
a highly adaptable nervous system that can be modified by activity and/or experience [12].
Because changes in synaptic strength are thought to underlie memory encoding and learning,
LTP is believed to play a critical role in these processes. In fact, most theories addressing
cognition regard LTP, and the reversal process long-term depression (LTD), as cellular
processes responsible for memory encoding [12, 17, 18]. In experimentally induced LTP,
brief high frequency bursts (e.g., ~100 Hz) of electrical stimulation initiate a long-lasting
increase in the strength of synaptic transmission [19]. Under in vitro experimental conditions,
applying short, high-frequency electrical stimuli to a synapse can strengthen, or potentiate,
the synapse for many minutes to several hours. In living animals, LTP presumably occurs
naturally or it can be induced experimentally and can last from hours to weeks. LTP has been
observed in both brain slice preparations in vitro and in living animals in vivo [20]. Past
studies have tried to directly link LTP with behavioral memory encoding, but most evidence
to date shows indirect associations [11, 12, 21, 22]. However, more direct associations
between hippocampal LTP and behaviorally defined memory have been recently shown [23,
24].
LTP and NMDA receptor activation
In most cases, LTP depends on N-methyl-D-aspartic acid (NMDA) receptor activation,
and increases in intracellular calcium [11, 25, 26]. Activation of the NMDA receptor requires
both glutamate and glycine binding and simultaneous depolarization of the cell membrane in
order to open the associated channel that allows calcium to flow into the cell [27]. The influx
of calcium through the NMDA receptor links NMDA receptor activation with calcium-
dependent intracellular signaling via a variety of intracellular pathways [28]. NMDA receptor
activation and NMDA-mediated downstream signaling is essential for normal synaptic
function. This key rise in intracellular calcium can also be mediated through other
mechanisms under different experimental conditions or in different cellular compartments
(e.g., dendritic spines, mossy fiber synapses) - for example, via voltage-sensitive calcium
channels [26, 29, 30] or release of calcium from intracellular stores [30]. However, most
attention has been given to calcium entry through the NMDA receptor complex; since the
NMDA channel opens only if there is simultaneous presynaptic glutamate release and
postsynaptic membrane depolarization, the NMDA receptor has been called a synaptic
