Biochemical, behavioural and electrophysiological investigations of brain maturation in chickens.

It is convenient to divide the development of synaptic networks into two phases: synapse formation during which synaptic contacts are established, and a subsequent maturation phase during which synaptic circuits are fine tuned and the properties of individual synapses are modified. Understanding the complex factors that control the protracted maturation process in humans is likely to be important for understanding a variety of neurological and psychiatric disorders. Chickens provide an ideal experimental model in which maturation specific changes can be identified and the mechanisms controlling them can be elucidated because the maturation phase is protracted and temporally separated from the formation phase. This paper reviews the knowledge about the biological mechanisms involved in the maturation phase of brain development in chickens and presents some new data. Studies of synaptic physiology suggest that maturation may alter the basal set point for stimulus induced synaptic plasticity. Biochemical and pharmacological studies of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and metabotropic glutamate receptors (mGluRs) revealed major changes in receptor regulation and the intracellular signalling pathways linked to receptor activation. Not surprisingly, therefore, when immature or mature chickens learn the same behavioural task the learning induced molecular events at the synapse are different. Changes in the features of auditory event related potentials and the basal EEG provide non-invasive techniques for monitoring maturation changes in chicken brain but prepulse inhibition (PPI) is too small and variable in chickens to be useful. Experimentally induced mild late-onset hypothyroidism retards some aspects of brain maturation and may help identify some of the mechanisms controlling maturation.

Maturational changes in the subunit composition of AMPA receptors and the functional consequences of their activation in chicken forebrain.

AMPA receptors play a critical role in synaptic plasticity and brain development. Here we show that Ca(2+) uptake in response to AMPA receptor activation decreases dramatically during maturation in chicken brain microslices without a change in tissue AMPA receptor content. We found that during maturation the relative concentration of GluR2 subunits increased, the concentration of the AMPA receptor-associated scaffold proteins SAP97 and GRIP decreased and that depolarization increased GluR1 phosphorylation at Ser831 in subcellular fractions enriched in postsynaptic densities at 2 weeks but not at 10 weeks. These changes are all consistent with a decreased Ca(2+) entry through AMPA receptor channels in response to receptor activation and may account for the changes in the functional properties of the receptor, which are thought to underlie, at least in part, the physiological changes that occur with maturation.