Biology Reference
In-Depth Information
0 or even positive mV) in VTA cells. As Hebb proposed, LTP requires concurrent presynaptic
activity and postsynaptic depolarization. Usually, the “tetanus” induces LTP, and subsequent
test stimulation evokes an EPSP that is much greater than during the initial baseline period. In
other words, the “tetanus” has modified the stimulated synapses so that they are more
effective. Other synaptic inputs into the same neuron that did not receive tetanic stimulation
do not show LTP. Hence, LTP is input specific. LTP is a form of synaptic plasticity and it is a
neurobiological mechanism for learning and memory.
Figure 2. LTP induction requires concurrent presynaptic activity and postsynaptic depolarization. A: In
the VTA dopaminergic neurons, two independent afferent pathways (P1, P2) were stimulated. P1
underwent the pairing protocol whereas P2 was not stimulated during the depolarization. B: Pairing
induced potentiation of P1 (LTP), while P2 remained unchanged. C: Example traces taken immediately
before and 20 minutes after pairing.
Cocaine acts as an addictive drug by increasing activity at dopamine neurons arising from
the VTA, the midbrain nucleus that is the origin of the mesolimbic and mesocortical
dopaminergic system. To study cocaine induced synaptic plasticity associated to LTP in the
VTA neurons, Ungless et al. (2001) treated rodents by injecting them with a single dose of
cocaine (experimental group) or saline (control group), and sacrificed them one day later.
EPSCs from dopamine neurons present in slices of the VTA of the midbrain were evoked
while holding neurons in voltage-clamp at +40 mV. The recorded EPSCs from animals
treated with cocaine were greater than those of control animals, indicating that cocaine was
able to induce LTP in the VTA synapses. LTP depends on NMDA receptor activation and the
subsequent induced increase in AMPA receptors (Dozmorov et al., 2006; Lu et al., 2001).
Ungless et al. (2001) also explored the relative contribution of AMPA and NMDA
receptors to EPSCs recorded in dopamine neurons. To do this, EPSCs were evoked both in
the absence and then the presence of NMDAR antagonist AP5, and an AMPAR/NMDAR
