1. Home
  2. Knowledge Base
  3. References
  4. Developmental disturbances in thalamocortical connection are sufficient to produce almost all features of schizophrenia.

Developmental disturbances in thalamocortical connection are sufficient to produce almost all features of schizophrenia.

Rajakumar R (2016) Developmental disturbances in thalamocortical connection are sufficient to produce almost all features of schizophrenia. Neuroscience 2016 Abstracts 845.01 / LLL41. Society for Neuroscience, San Diego, CA.

Summary: Partial ablation of subplate of the developing frontal cortex was achieved by two different approaches in PD1 S-D rat pups: infusions of either P75 receptor antibody-conjugated to saporin or β-nerve growth factor, and both resulted in identical changes: ~20% loss of subplate and aberrant distribution of thalamocortical fibers within the cortex. Control littermates received similar infusions of vehicle. Pups were allowed to grow under standard care. All animals survived, and showed no noticeable differences in milestones or activities. No differences were observed between lesioned and control groups in standard behavioral tests at 6-8 weeks of age. However, lesioned group showed significantly increased stress- or amph-induced locomotor activity, PPI deficit, social interaction deficits, and executive functional deficits after 9 weeks of age. A month-course of haloperidol or risperidon completely ameliorated locomotor abnormalities but did not affect social interaction deficit. Histological examination revealed several interesting changes: (1) 18% loss of gray matter thickness in the mPFC and no change in thickness in other cortical areas at 12 weeks, while at 20 weeks PFC loss remained at 18% but parietal and temporal cortices showed progressive thinning (20-36%); (2) significant loss of neuropil in the mPFC characterized by loss of synaptophysin and spinophilin labeling; (3) no changes in the number of neuronal cell bodies in PFC; (4) significantly increased lateral and third ventricular volume; (5) significant loss of dopaminergic fibers in lower layers of the PFC; (6) significant loss of GAD67-IR terminals in PFC; (6) significant decrease in the intensity of PAR labeling and abnormal distribution of PAR-IR terminals/cell bodies without loss of neurons; (7) significant loss of GAT-1-IR terminals only in upper layers of the PFC; (8) loss of PAR-IR terminals and cell bodies in the hippocampus; (9) abnormal distribution but no loss of CR-IR neurons in the entorhinal cortex; and (10) significantly reduced volume of basolateral amygdala. No changes were seen in ChAT neurons of the septum or N. basalis. All structural changes noted above were seen as early as 12 weeks and were not affected by antipsychotic treatment between 12 and 16 weeks. Results suggest that disturbances in thalamocortical pathfinding (due to genetic or other mechanisms) are sufficient to cause features of schizophrenia in normal animals.

Related Products: 192-IgG-SAP (Cat. #IT-01)