Biology Reference
In-Depth Information
(b) LTP induction
In spite of early reports that tetanic stimulation evokes LTP (Hirsch and Crepel 1990;
1991; Law-Tho et al. 1995), subsequent studies have been unable to replicate this finding
(Vickery et al. 1997; Otani et al. 1998). However, more recent studies have evoked LTP in
the mPFC by using very high frequency tetanic stimulation, by using a burst stimulation
protocol instead of tetanic stimulation, or by “priming” the mPFC with a prior application of
dopamine. These are discussed below.
Theta burst stimulation (4 stimuli at 100 Hz, repeated 10 times at 5 Hz) has been found to
be effective in evoking LTP following stimulation of superficial layers (Vickery et al. 1997;
Morris et al. 1999; Otani and Kolomiets 2003) and deep layers of the mPFC (Vickery et al.
1997; Morris et al. 1999; Young and Yang 2005) but not following stimulation of layer 3
(Young and Yang 2005). This form of LTP is mediated by mGluRs since it is blocked by the
MCPG (Vickery et al. 1997) and facilitated by the group 1 mGluR agonist
dihydroxyphenylglycine (DHPG; Morris et al. 1999). During burst stimulation more action
potentials and a larger depolarisation are evoked than during tetanic stimulation (Otani and
Kolomiets 2003), likely leading to a greater increase in calcium, and thereby facilitating the
induction of LTP (Dudek and Bear 1992; Artola and Singer 1993; Hansel et al. 1996;
Cormier et al. 2001). Alternatively, LTP may be evoked more readily under these conditions
because short bursts of stimulation “prime” the dendrites to optimise NMDA receptor
activation (Larson and Lynch 1988). However in the presence of dopamine, burst firing
evoked LTD (Otani and Kolomiets 2003).
LTP is also evoked in rodent layer 5 field EPSPs by very high tetanic stimulation of layer
2 (300 Hz for 0.5 second). Delivering the tetanic stimulation once evokes LTP that persists
for approximately 60 minutes (early phase LTP), while delivering the tetanus five times
evokes LTP that is sustained for 3 hours (late phase LTP; Huang et al. 2004). Late phase LTP
is blocked by AP5 and anisomycin, and attenuated by a D1 receptor antagonist, while early
phase LTP is converted to late phase LTP in the presence of a D1 receptor agonist. This
suggests that D1 receptor activation is required for long lasting LTP. Consistent with this, in
D1 heterozygote knockout mice application of a D1 agonist failed to convert early phase LTP
to late phase LTP (Huang et al. 2004).
In agreement with the above finding that dopamine facilitates LTP, dopamine release
following stimulation of the ventral tegmental area (VTA) combined with tetanic stimulation
leads to LTP in vivo (Gurden et al, 1999; 2000). However this contrasts with experiments
coupling low frequency tetanic stimulation (50 Hz) with dopamine exposure in vitro (Otani et
al. 1998), which evokes LTD. This discrepancy may be due to the very low ambient
dopamine concentrations in vitro compared to a substantial background dopamine tone in
vivo (Takahata and Moghaddam 2000). Consistent with this, transient exposure to dopamine
in vitro, prior to tetanic stimulation, leads to LTP, when the 50 Hz tetanic stimulation is
subsequently delivered in the presence of dopamine (Blond et al. 2002; Matsuda et al. 2006).
This was not due to enhanced postsynaptic depolarisation during the LTP protocol following
“priming”, since this was actually less than that observed when LTD was evoked. Instead this
“priming” effect of dopamine application requires activation of both D1 and D2 receptors
(Matsuda et al. 2006), and may be due to metaplastic changes (Abraham and Bear 1996).
Applying AP5 during “priming” or during the tetanus blocks LTP, as does buffering
intracellular calcium or hyperpolarising the cell during the LTP induction protocol (Matsuda
