Biology Reference
In-Depth Information
In addition, synaptic plasticity in the PFC may also depend on the membrane potential of
layer 5 pyramidal neurons. Under anaesthesia, neurons in the PFC exhibit a bistability in
vivo, oscillating between up and down states at a frequency of approximately 1 Hz
(Branchereau et al. 1996; Lewis and O'Donnell 2000). Furthermore, stimulation of the VTA,
which releases dopamine into the mPFC, triggers up states (Lewis and O'Donnell 2000).
Since during in vitro slice recordings the resting membrane potential mimics a down state,
this may be an explanation for the greater ease of evoking LTD than LTP with tetanic
stimulation (Law-Tho et al. 1995; Otani et al. 1998; Takita et al. 1999). In contrast, LTP may
be more likely to be evoked from depolarised potentials that mimic the up state in vivo
(Gurden et al. 1999; Gurden et al. 2000), due to greater activation of NMDA receptors at
these membrane potentials.
(ii) PFC-hippocampal connections
The CA1 region of the hippocampus, apart from the most dorsal region, together with the
subiculum, send direct inputs via the fornix and fimbria to the prelimbic, infralimbic, lateral,
and medial orbital areas of the mPFC (Jay and Witter 1991). Hippocampal fibres innervate all
cell layers of the mPFC, but most densely innervate layer 5 of the prelimbic mPFC in an
ipsilateral and unidirectional manner (Sesack et al. 1989). Hippocampal fibres form
asymmetrical synapses on dendritic spines of pyramidal neurons and on dendrites of
GABAergic interneurons (Carr and Sesack 1996; Gabbott et al. 2002; Tierney et al. 2004),
where they release glutamate to activate AMPA and NMDA receptors to evoke an EPSP with
a latency of approximately 16 ms (Jay et al. 1992; Gigg et al. 1994; Thierry et al. 2000;
Degenetais et al. 2003). Intracellular recordings in vivo have shown that stimulation of CA1
can evoke complex EPSP/ inhibitory postsynaptic potential (IPSP) waveforms in pyramidal
neurons in the prelimbic mPFC (Degenetais et al. 2003), presumably via disynaptic activation
of pyramidal neurons and interneurons. Inputs from the hippocampus have been shown to
provide information about context during extinction of fear memories (see below; Kim and
Fanselow 1992; Phillips and LeDoux 1992), and spatial working memory (see below;
Floresco et al. 1997; Seamans et al. 1998), and LTP at inputs to the prelimbic mPFC in the
awake rat can last for days (Doyere et al. 1993; Jay et al. 1996). As well as being crucial for
the retrieval of stored information during working memory tasks, hippocampal inputs are also
important for the generation of up and down states in the mPFC, since lesioning of the ventral
hippocampus prevents up transitions in the mPFC (O'Donnell et al. 2002).
Plasticity at inputs from the hippocampus, including those travelling via the subiculum,
has been well studied, with the function of plasticity at these synapses thought to be involved
in stabilising the storage of learned events in the cortex, and with providing retrospective
information for future planning (Goto and Grace 2007). High frequency stimulation of the
ventral hippocampus (250 Hz in bursts of 200 ms) evokes LTP of field EPSP recorded in the
deep layers of the prelimbic mPFC in vivo (Jay et al. 1995; Laroche et al. 2000; Hotte et al.
2007), and LTP of both EPSPs and IPSPs recorded intracellularly (Degenetais et al. 2003),
which persists for several hours in both anaesthetised animals and awake freely moving
animals (Jay et al. 1996). Similarly, tetanic stimulation of the fornix also evokes LTP in the
prelimbic mPFC (Mulder et al. 1997). This form of LTP requires activation of NMDA
