A modeling study suggesting how a reduction in the context-dependent input on CA1 pyramidal neurons could generate schizophrenic behavior.

The neural mechanisms underlying schizophrenic behavior are unknown and very difficult to investigate experimentally, although a few experimental and modeling studies suggested possible causes for some of the typical psychotic symptoms related to this disease. The brain region most involved in these processes seems to be the hippocampus, because of its critical role in establishing memories for objects or events in the context in which they occur. In particular, a hypofunction of the N-methyl-D-aspartate (NMDA) component of the synaptic input on the distal dendrites of CA1 pyramidal neurons has been suggested to play an important role for the emergence of schizophrenic behavior. Modeling studies have investigated this issue at the network and cellular level. Here, starting from the experimentally supported assumption that hippocampal neurons are very specific, sparse, and invariant in their firing, we explore an experimentally testable prediction at the single neuron level. The model shows how and to what extent a pathological hypofunction of a context-dependent distal input on a CA1 neuron can generate hallucinations by altering the normal recall of objects on which the neuron has been previously tuned. The results suggest that a change in the context during the recall phase may cause an occasional but very significant change in the set of active dendrites used for feature recognition, leading to a distorted perception of objects.