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

Institute of Biophysics, National Research Council, Palermo, Italy.
Neural networks: the official journal of the International Neural Network Society (Impact Factor: 2.71). 08/2011; 24(6):552-9. DOI: 10.1016/j.neunet.2011.01.001
Source: PubMed


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.

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    • "Interestingly, the computational model proposed by Hoffman showed that this dysfunction was maximized if the retrieval cues were not similar to the stored memory and if the number of synapses on to each neuron was reduced, resulting in decreased system capacity. In agreement with these results was the computational evidence that alterations of the distal input of CA1 pyramidal neurons in the hippocampus could generate hallucinations by altering the normal recall of objects on which the neurons have been previously tuned (Migliore et al. 2011 ) . Finally, these models of excessive pruning constitute an interesting way to account for the emergence of auditory-verbal hallucinations during a speci fi c developmental window, such as adolescence, which is the peak incidence period for schizophrenia (Paus et al. 2008 ; Rolls and Deco 2011 ) . "
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