Abnormal medial prefrontal cortex connectivity and defective fear extinction in the presymptomatic G93A SOD1 mouse model of ALS

• Published in: Genes, brain and behavior Vol. 7; no. 4; pp. 427 - 434
• Main Authors: Sgobio, C., Trabalza, A., Spalloni, A., Zona, C., Carunchio, I., Longone, P., Ammassari‐Teule, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-2008
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - complications; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - psychology; Animals; Cell Shape - genetics; Cognition Disorders - enzymology; Cognition Disorders - genetics; Cognition Disorders - physiopathology; Conditioning (Psychology) - physiology; dendritic arbor; dendritic spines; Dendritic Spines - pathology; Disease Models, Animal; Disease Progression; Extinction, Psychological - physiology; Fear - physiology; fear extinction; Genetic Predisposition to Disease; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation - genetics; Nervous System Malformations - enzymology; Nervous System Malformations - genetics; Nervous System Malformations - physiopathology; Neural Pathways - abnormalities; Neural Pathways - enzymology; Neural Pathways - physiopathology; prefrontal cortex; Prefrontal Cortex - abnormalities; Prefrontal Cortex - enzymology; Prefrontal Cortex - physiopathology; Pyramidal Cells - pathology; Silver Staining; Superoxide Dismutase - genetics
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/j.1601-183X.2007.00367.x

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neuropathy associated with the degeneration of spinal and brainstem motor neurons. Although ALS is essentially considered as a lower motor neuron disease, prefrontal cortex atrophy underlying executive function deficits have been extensively reported in ALS patients. Here, we examine whether prefrontal cortex neuronal abnormalities and related cognitive impairments are present in presymptomatic G93A Cu/Zn superoxide dismutase mice, a mouse model for familial ALS. Structural characteristics of prelimbic/infralimbic (PL/IL) medial prefrontal cortex (mPFC) neurons were studied in 3‐month‐old G93A and wild‐type mice with the Golgi–Cox method, while mPFC‐related cognitive operations were assessed using the conditioned fear extinction paradigm. Sholl analysis performed on the dendritic material showed a reduction in dendrite length and branch nodes on basal dendrites of PL/IL neurons in G93A mice. Spine density was also decreased on basal dendrite segments of branch order five. Consistent with the altered morphology of PL/IL cortical regions, G93A mice showed impaired extinction of conditioned fear. Our findings indicate that abnormal prefrontal cortex connectivity and function are appreciable before the onset of motor disturbances in this model.