Developmental Changes in Structural and Functional Properties of Hippocampal AMPARs Parallels the Emergence of Deliberative Spatial Navigation in Juvenile Rats

Abstract

The neural mechanisms that support the late postnatal development of spatial navigation are currently unknown. We investigated this in rats and found that an increase in the duration of AMPAR-mediated synaptic responses in the hippocampus was related to the emergence of spatial navigation. More specifically, spontaneous alternation rate, a behavioral indicator of hippocampal integrity, increased at the end of the third postnatal week in association with increases in AMPAR response duration at SC-CA1 synapses and synaptically driven postsynaptic discharge of CA1 pyramidal neurons. Pharmacological prolongation of glutamatergic synaptic transmission in juveniles increased the spontaneous alternation rate and CA1 postsynaptic discharge and reduced the threshold for the induction of activitydependent synaptic plasticity at SC-CA1 synapses. A decrease in GluA1 and increases in GluA3 subunit and transmembrane AMPAR regulatory protein (TARP) expression at the end of the third postnatal week provide a molecular explanation for the increase in AMPAR response duration and reduced efficacy of AMPAR modulators with increasing age. A shift in the composition of AMPARs and increased association with AMPAR protein complex accessory proteins at the end of the third postnatal week likely "turns on" the hippocampus by increasing AMPAR response duration and postsynaptic excitability and reducing the threshold for activitydependent synaptic potentiation.

Ontogeny of memory: An update on 40 years of work on infantile amnesia

“…This transition marks what we believe should be considered nearing the end of infancy (equivalent to 0-abilities (large-scale maze navigation) do not fully emerge in human children until around 7 years of age [53]. In rats, consistent performance in equivalent spatial or configurational learning and memory tasks emerges at the end of the third postnatal week (P21) [54][55][56]. In light of this we consider P12-P21 to more accurately represent the juvenile period, to reflect young childhood in humans.…”

“…Am J Anat. 1957;100:241-67. abilities; P10 is the age at which rats first explore the extra-nest environment and acquire odour aversion learning as the amygdala matures [51,52]; maturation of hippocampal-dependent spatial abilities occurs at the end of the 3rd postnatal week [53][54][55][56]59]; the 4th postnatal week signals the peak of the growth spurt [59], emergence of adolescent behaviours such as increased time spent in social interaction and play behaviour [57,58] and reproductive and hormonal changes [202,203]. Infant (red); juvenile (orange); preadolescent (yellow); adolescent (green); adult (blue).…”

Synaptic AMPA receptor composition in development, plasticity and disease

“…Furthermore, there is another shift in the composition of AMPARs by P21, as GluA3 levels increase and GluA1 levels decline. Since AMPARs containing GluA3 show reduced deactivation and desensitization compared to GluA1-containing AMPARs 70 , this likely accounts for the developmental increase in the duration of AMPAR responses, postsynaptic excitability and the reduction in LTP threshold 71 .…”

Developmental studies of the hippocampus and hippocampal-dependent behaviors: Insights from interdisciplinary studies and tips for new investigators

“…In rodents, as judged by performance in spatial learning and memory tasks, the hippocampus does not show signs of adult-like function until at least the end of the third postnatal week (Blair et al, 2013; Douglas et al, 1973; Dumas, 2004; Kraemer and Randall, 1995; Rudy et al, 1987). Reliance of spatial learning and memory on well-developed motor and distal sensory systems (Rudy, 1992) may partially explain why the hippocampus matures late in the postnatal period, so that information fed to the juvenile hippocampus is an accurate, high fidelity representation of the environment (Fagiolini et al, 1994; Göb et al, 1987; Schachtele et al, 2011; Stanton, 2000).…”