It should be noted that inhibitory synapses

themselves may express experience-dependent 5-FU nmr plasticity (Brosh and Barkai, 2009), further helping shape coding of familiar odors. In summary, as in other systems, piriform cortical synaptic inhibition serves to shape receptive fields, sensory evoked responses and the temporal structure of cell output. Inhibitory neurons are not only targeted by afferent and intracortical excitatory inputs but are also the targets of inputs from other regions (V.M. Luna, 2011, Assoc. Chemorecetion Sciences, abstract; Mouly and Di Scala, 2006) and neuromodulators (Neville and Haberly, 2004). Thus, this suggests a role for inhibition in modulating cortical processing in a state- or experience-dependent manner. The olfactory cortex is the target of neuromodulatory input from the noradrenergic nucleus locus coeruleus, the cholinergic nucleus of the horizontal limb of the diagonal band and the serotonergic raphe nucleus (Shipley and Ennis, 1996). These modulatory inputs shape cortical

processing and circuit plasticity. For example, activation of the locus coeruleus enhances odor evoked responses and respiratory entrainment of piriform cortical neurons to the respiratory cycle (Bouret and Sara, 2002). This enhancement may have PF-06463922 concentration multiple contributing mechanisms, including NE effects in the olfactory bulb (Jiang et al., 1996), modulation of cortical association fiber synaptic efficacy (Hasselmo et al., 1997), and the cortical dishabituation mechanism described above (Smith et al., 2009). It nonetheless demonstrates

the importance of behavioral state and noradrenergic tone on piriform cortical activity. ACh similarly modulates activity and plasticity in the piriform cortex. ACh to the olfactory bulb and olfactory cortex derives from the horizontal limb of the diagonal band, as opposed to the medial septum which is the primary cholinergic input to the entorhinal cortex and hippocampal formation. Cholinergic muscarinic receptor activation selectively suppresses intrinsic association fiber synapses, with minimal effect on afferent fiber synapses (Hasselmo and Bower, 1992). ACh also modulates pyramidal very cell excitability (Barkai and Hasselmo, 1994) and association fiber synaptic plasticity (Hasselmo and Barkai, 1995 and Patil et al., 1998). Disruption of normal cholinergic activity within the piriform cortex impairs odor memory and discrimination of similar odors (De Rosa and Hasselmo, 2000, Fletcher and Wilson, 2002, Linster et al., 2001, Ravel et al., 1992, Saar et al., 2001 and Wilson, 2001). The piriform cortex encompasses the largest area within the olfactory cortex, and thus has received the most experimental attention.