Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains.

The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7-46 years of age) were stained using a Golgi-Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age-matched TD controls (<18 years old) and (b) decreases in the amygdala as people with ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age-matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD.

The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wild type mice in the 5-Choice Serial Reaction-Time Task.

Genetically-altered mice, lacking functional NK1 receptors (NK1R-/-), express abnormal behaviours that are prominent in Attention Deficit Hyperactivity Disorder: namely, inattentiveness and impulsivity (indicated by their greater % omissions and premature responses in the 5-Choice Serial Reaction-Time Task (5-CSRTT) and locomotor hyperactivity. We investigated how behaviour in the 5-CSRTT is affected by repeated testing and whether the abnormalities expressed by NK1R-/- mice are mimicked by treating wild type mice with a NK1R antagonist (L 733060 or RP 67580; 5 or 10 mg/kg). Repeated testing with a variable (VITI) or fixed, prolonged (LITI) intertrial interval reduced % omissions. Premature responses also declined, but only in NK1R-/- mice, in the VITI test. By contrast, perseveration increased in both genotypes. RP 67580 (10 mg/kg) increased the % omissions in both genotypes in the VITI, an action which cannot be attributed to NK1R antagonism. Neither drug affected perseveration. However, for premature responses, the response profile suggested that the low and high doses of RP 67580 (VITI) and L 733060 (LITI) had opposing effects on this behaviour. We infer that the effect of NK1R antagonists in the 5-CSRTT is confounded by animals' test experience and non-specific drug effects at sites other than NK1R, possibly L-type Ca²âº(v) channels.