Biology Reference
In-Depth Information
stimulation (15 action potentials at 50 Hz, repeated 4 times), following baseline stimulation at
0.5 Hz (Wang et al. 2006). This could be attributable to the greater number of tetanic
repetitions given, or alternatively could be suggestive of a distinct synaptic subtype in the
ferret, since it only occurred at facilitating synapses. PTP evoked in the rat was enhanced by a
dopamine type-1 (D1) receptor antagonist (Young and Yang 2005), suggesting that
endogenous release of dopamine during the induction protocol suppresses PTP, presumably
via a presynaptic suppression of glutamate release (Gao et al. 2001; Seamans et al. 2001). In
contrast STP was suppressed by a D1 antagonist at layer 5 inputs, instead revealing long-term
depression (LTD), and thereby suggesting a requirement for endogenous dopamine to evoke
both STP and long-term potentiation (LTP; see below). In vivo, STP is reduced by both D1
and dopamine type-2 (D2) receptor antagonists, following stimulation of the superficial layers
of the PFC with trains of stimuli at 40 Hz (Goto and Grace 2007).
Facilitating or depressing synapses behave as high- and low-band filters, respectively,
endowing a postsynaptic neuron with an optimum frequency range for presynaptic inputs
(Fuhrmann et al. 2002). Furthermore, synaptic augmentation allows neurons in the mPFC to
reach action potential threshold repetitively during activation of recurrent synapses. Computer
simulations have shown that a balance between augmentation and synaptic depression is
important for sustaining persistent activity at a level observed in vivo in behaving animals
during working memory tasks (approximately 50 Hz) (Funahashi et al. 1989). Consistent with
this, during synaptic depression evoked with a “natural” spike train i.e. with a variable
temporal pattern of firing mimicking in vivo recordings, postsynaptic depolarisation is
maintained (Gonzalez-Burgos et al. 2004). Such diversity in short-term plasticity exhibited by
pyramidal neuron synapses in the mPFC is likely to be advantageous for its role in executive
function and mnemonic processing, since it allows greater flexibility than, for example, LTP,
and has a lesser metabolic load. Short-term plasticity also enables rapid switching of
attention, essential for the functioning of the PFC in cognitive processing.
4.
L
ONG
-T
ERM
P
LASTICITY
As well as being important in working memory, the PFC is also important in long-term
memories, such as declarative memory in humans and associative learning in rodents (see
below) (Otani 2002). As in other brain regions, the process underlying the formation of these
memories is thought to be synaptic plasticity. The next section will describe what is known
about the mechanisms underlying long-term synaptic plasticity in the prelimbic mPFC.
(i) LTP and LTD in the PFC
Early studies examining plasticity at layer 2/3 and layer 5 inputs to layer 5 pyramidal
neurons found that at synapses where plasticity could be evoked, which constituted
approximately two thirds of synapses, either LTP or LTD was elicited in relatively equal
proportions (Hirsch and Crepel 1990; 1991; Law-Tho et al. 1995; Auclair et al. 2000;
Guzman et al. 2005). This was induced by tetanic stimulation (4 trains of stimuli at 50-100
Hz for 1-2 seconds) in the presence of GABAergic blockers. LTP and LTD evoked in this
