Delayed onset of post-natal expression of plasticity related immediate early gene Arc in medial entorhinal cortex grid cell network.
1. ARL NSMA
2. Evelyn F. McKnight Brain Inst., Univ. Arizona, Tucson, AZ
Superficial medial entorhinal cortical neurons project to the hippocampus, and exhibit a striking spatial firing pattern in the form of regularly repeating, triangular grids of elevated activity ('grid cells'). It has been suggested that the synaptic organization underlying such behavior might be self-organized during early post-natal development, before rat pups exhibit significant exploratory behavior, but there is very little published data on the development of the intrinsic circuitry of this structure. Arc (activity-regulated cytoskelatal protein) is a synaptic plasticity related immediate early gene (IEG) that is expressed after synaptic activity and participates in AMPA receptor trafficking. Increased transcription of Arc mRNA occurs in the hippocampus and neocortex after spatial exploration, and it is presumed that Arc is specifically transcribed by the neurons that were active during the behavior. Additionally, maximal electroconvulsive shock (MECS), which elicits seizure-like activity, activates Arc transcription in a large proportion of adult hippocampal and neocortical neurons and has been used as an indicator of Arc expression competence. In the developing rat brain, the time course of plasticity varies across different brain regions, possibly regulating the development of the correct connectivity in those regions. For example, Vendrell et. al. (1998) observed that the IEG cFos is expressed following seizure in the hippocampus of neonatal mice only after a certain age, with different subregions of the hippocampus becoming active at different times.
To study the timecourse of the development of synaptic plasticity mechanisms, we used fluorescent in situ hybridization to label the expression of Arc mRNA in the brains of rat pups aged 6-15 days, 5 minutes after MECS. Neurons in CA1, CA3, subiculum, and deep layers (V-VI) expressed Arc at about 80% of the adult level by day 6 and reached asymptote by day 15. By contrast, CA2, all layers of dorsal neocortex, the superficial layers of EC (II-III) and the DG were only at about 20% of adult levels by day 6 and were still increasing at day 15. Interestingly, the free-blade of the DG did not express any Arc at day 6 and the attached-blade showed a clear lamination pattern in which Arc was expressed only in the upper region of the layer. Lamination was still visible at day 15. Rat pups show a gradual increase in exploratory behavior after about day 9. The present data thus suggest that activity dependent synaptic plasticity in the grid cell network might be delayed until after the onset of active spatial exploration and hence these circuits may potentially be more dependent on behavior than hippocampal circuits.
Grant/Other Support: NS020331; AG009219; NS054465; BIO5 Institute
Keyword (Complete): path integration; development; AMPA receptor