Similar to other brain regions, both α7 and non-α7 nAChR signaling pathways converge in the PFC to modulate both excitatory and inhibitory neurotransmission (see Figure 2). Although glutamatergic pyramidal cells in layer V lack nAChRs, nicotine increases EPSCs and Glutamate release from thalamo-cortical afferents that do express them (Gioanni et al., 1999; Lambe et al., 2003; Couey et al., 2007). There are two populations of GABAergic interneurons, fast spiking and non-fast spiking, with only the latter bearing nAChRs (α7 and α4β2*) (Gabbott et al., 1997; Kawaguchi and Kondo, 2002). Activation of both α7 and β2-containing nAChRs on glutamatergic nerve endings enhance the release of excitatory amino acids but do so by different mechanisms (Dickinson et al., 2008). α7 nAChRs, predominately found on ryanodine positive terminals, mediate release by calcium-induced calcium release (CICR) which is coupled to the activation of pre-synaptic extracellular signal-regulated kinase (ERK2) and phosphorylation of synapsin-1. Non-α7 nAChRs recruit voltage-gated calcium channels to induce release of [3H] D-aspartate (Dickinson et al., 2008). Additionally, β2-containing nAChRs govern glutamatergic neurotransmission and activation of this receptor subtype by nicotine enhances glutamate release onto layer 5 and 6 pyramidal neurons (Gioanni et al., 1999; Lambe et al., 2003).
