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NMDA Receptor Activation and Calcium Influx
Glutamate only
Glutamate + Depolarization
Mg ++
- 65 mV
- 30 mV
- 30 mV
Segregation of Retinal Terminals in the Three-eyed Frog
NMDA Receptor Blockade
NMDA Receptor Activation
FIGURE 9.27 NMDA receptors are involved in synaptic plasticity. A. The NMDA receptor is activated by
a combination of glutamate binding and membrane depolarization. A positively charged magnesium ion
blocks the NMDA receptor channel at rest. Depolarization causes the magnesium ion to be ejected, and this
permits sodium and calcium ions to flow in. B. When a third eye is implanted into a frog embryo, the tectum
becomes co-innervated by two eyes. The afferents from each eye segregate into stripes, similar to primary
visual cortex (left). When three-eyed frogs are treated with an NMDA receptor antagonist (either APV or
MK801), the afferents do not segregate, and stripe formation is prevented (middle). When three-eyed frogs
are treated with NMDA, stripe formation is enhanced (right), and the borders between stripes is sharper.
(Adapted from Cline et al., 1987; Cline and Constantine-Paton, 1990)
systems. For example, we learned that monocular lid
closure weakens synapses in the cortex that are driven
by the deprived eye. However, when the same manip-
ulation is performed during the chronic infusion of a
NMDAR blocker, the strength of “deprived” synapses
is preserved (Kleinschmidt et al., 1987). Thus, synapses
from the open eye activate NMDARs in the cortex,
allowing calcium to enter postsynaptic neurons.
We will consider what calcium might be doing once it
enters the postsynaptic neuron below.
NMDA receptors turn out to be broadly involved in
the stability of developing excitatory synapses. In the
cerebellum, where adult Purkinje cells are innervated
by one climbing fiber, the chronic administration of a
NMDAR blocker (AP5) results in 50% of Purkinje cells
remaining multiply innervated (Rabacchi et al., 1992).
In frogs, the innervation pattern of retinal afferents can
be disrupted by NMDAR blockers. For example, when
an extra eye is transplanted into a tadpole, the retinal
axons project to the midbrain and form a “striped”
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