Visual paired association learning is dependent upon the integrity of the hippocampus and cortical areas of the medial temporal lobe (MTL) (Murray et al., 1993). These areas, which include the entorhinal, perirhinal and parahippocampal cortices,

receive inputs from and are a source of feedback to IT cortex (see Figure 2; Webster et al., 1991). The learning impairment following MTL lesions appears to be one of memory formation and the MTL selleck areas are thus, under normal conditions, believed to exert their influence by enabling structural reorganization of local circuits in the presumed site of storage, i.e., IT cortex (Miyashita, 1993, Squire et al., 2004 and Squire and Zola-Morgan, 1991). This hypothesis is supported by the finding that MTL lesions also eliminate the formation of pair-coding responses in IT cortex (Higuchi and Miyashita, 1996). Exactly how MTL regions contribute to the strengthening of connections between the neuronal representations of paired stimuli—with the attendant associative learning and neuronal response changes—is unknown. There are, nonetheless,

good reasons to suspect the involvement of a Hebbian mechanism for enhancement of synaptic efficacy. Specifically, the temporal coincidence of stimuli during learning may cause coincident patterns of neuronal activity, which may lead, in turn, to a strengthening of synaptic connections between the neuronal representations of the paired stimuli (e.g., Yakovlev et al., 1998). This conclusion is supported by the finding that associative Bosutinib in vivo plasticity in IT cortex is correlated with the appearance of molecular-genetic markers for synaptic isothipendyl plasticity: mRNAs encoding for brain-derived neurotrophic factor (BDNF) and for the transcription factor zif268 (Miyashita et al., 1998 and Tokuyama et al., 2000). BDNF is known to play a role in activity-dependent synaptic plasticity (Lu, 2003). zif268 is a transcriptional regulator that leads to gene products necessary for structural changes that underlie plasticity (Knapska and Kaczmarek, 2004). The inferior temporal cortex was chosen as the initial

target for study of associative neuronal plasticity for a number of reasons. This region of visual cortex was, for many years, termed “association cortex.” Although this designation originally reflected the belief that the temporal lobe represents a point at which information from different sensory modalities is associated (Flechsig, 1876), the term was later used to refer, more generally, to the presumed site of Locke’s “association of ideas. This view received early support from neuropsychological studies demonstrating that temporal lobe lesions in both humans and monkeys selectively impair the ability to recognize visual objects, while leaving basic visual sensitivities intact (Alexander and Albert, 1983, Brown and Schafer, 1888 and Kluver and Bucy, 1939; Lissauer, 1988).