Learning to associate the context in which a stimulus occurs is an important aspect of animal learning. We propose that the association of an olfactory stimulus with its multisensory context is mediated by projections from ventral hippocampus (vHC) networks to the anterior olfactory nucleus (AON). Using a contextually cued olfactory discrimination task, rats were trained to associate 2 olfactory stimuli with different responses depending on visuospatial context. Temporary lesions of the AON or vHC impaired performance on this task. In contrast, such lesions did not impair performance on a noncontextual olfactory discrimination task. Moreover, vHC lesions also impaired performance on an analogous contextually cued texture discrimination task, whereas AON lesions affected only olfactory contextual associations. We describe a distinct role for the AON in olfactory processing and conclude that early olfactory networks such as the olfactory bulb and AON function as multimodal integration networks rather than processing olfactory signals exclusively.

Axon guidance molecules and neuronal activity have been implicated in the establishment and refinement of neural circuits during development. It is unclear, however, whether these guidance molecule-and activity-dependent mechanisms interact with one another to shape neural circuit formation. The formation of corticospinal (CS) circuits, which are essential for voluntary movements, involves both guidance molecule-and activity-dependent components during development. We previously showed that semaphorin6D (Sema6D)-plexinA1 (PlexA1) signaling eliminates ipsilateral projections of CS neurons in the spinal cord, while other studies demonstrate that CS projections to the spinal cord are eliminated in an activity-dependent manner. Here we show that inhibition of cortical neurons during postnatal development causes defects in elimination of ipsilateral CS projections in mice. We further show that mice that lack the activity-dependent Bax/Bak pathway or caspase-9 similarly exhibit defects in elimination of ipsilateral CS projections, suggesting that the activity-dependent Bax/Bak-caspase-9 pathway is essential for the removal of ipsilateral CS projections. Interestingly, either inhibition of neuronal activity in the cortex or deletion of Bax/Bak in mice causes a reduction in PlexA1 protein expression in corticospinal neurons. Finally, intracortical microstimulation induces activation of only contralateral forelimb muscles in control mice, whereas it induces activation of both contralateral and ipsilateral muscles in mice with cortical inhibition, suggesting that the ipsilaterally projecting CS axons that have been maintained in mice with cortical inhibition form functional connections. Together, these results provide evidence of a potential link between the repellent signaling of Sema6D-PlexA1 and neuronal activity to regulate axon elimination.

AbstractLearning to associate the context in which a stimulus occurs is an important aspect of animal learning. We propose that the association of an olfactory stimulus with its multisensory context is mediated by projections from ventral hippocampal networks (vHC) to the anterior olfactory nucleus (AON). Using a contextually-cued olfactory discrimination task, rats were trained to associate two olfactory stimuli with different responses depending on visuo-spatial context. Temporary lesions of the AON or vHC impaired performance on this task. In contrast, such lesions did not impair performance on a non-contextual olfactory discrimination task. Moreover, vHC lesions also impaired performance on an analogous contextually-cued texture discrimination task, whereas AON lesions affected only olfactory contextual associations. We describe a distinct role for the AON in olfactory processing, and conclude that early olfactory networks such as the olfactory bulb and AON function as multimodal integration networks rather than processing olfactory signals exclusively.Significance statementContextual information has long been known to play a key role in cognitive functions such as memory and decision making. We here show the contextual modulation of neural information in early primary sensory networks and its effects on contextually conditional learned behavior. We propose that projections from ventral hippocampus to anterior olfactory nucleus convey contextual information to the early olfactory system, modulating sensory representations and olfactory perception. Using behavioral pharmacology and computational modeling, we show how established network structures can mediate multimodal information and use context to make olfactory decisions.