Postnatal Development of Glutamate Receptor-Mediated Responses in the Neostriatum

Abstract

Three experimental approaches were used to examine the maturation of N-methyl-D-aspartate (NMDA) receptors in the neostriatum and compare their developmental profile to that of the non-NMDA receptors [α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate (KA)]. The first, and least conventional approach utilized infrared videomicroscopy to measure NMDA-induced swelling in single cells in a brain slice. The results demonstrated that NMDA receptors display an incremental pattern of postnatal development with no responses at postnatal day (PND) 3, weak responses at PND 7, the largest responses by PND 14 and slight decreases at PNDs 21 and 28. At PNDs 3 and 7, KA-induced cell swelling was proportionately greater than NMDA-induced cell swelling suggesting earlier maturation of this non-NMDA receptor subtype. The second approach used whole-cell patch clamp analysis to examine NMDA currents and compare their maturation to AMPA/KA-induced currents. Though the data are still preliminary, a very similar developmental pattern emerged. NMDA-induced currents were small and developed slowly after PND 7. In contrast, AMPA/KA-induced currents were larger and appeared to develop earlier. Finally, dizocilpine (MK-801) binding was measured in homogenates of neostriatal tissue. The ontogeny of binding resembled a step function with increases between PNDs 3 and 7 and PNDs 14 and 21. Binding peaked at PND 28 and then declined slightly in the adult (PND 60). The affinity of MK-801 for the receptor did not change during postnatal development. These findings demonstrate the pattern of functional development of glutamate receptors in the neostriatum. The NMDA receptor subtype displays minimal functional development until PND 14. In contrast, neostriatal AMPA/KA receptor function appears to precede NMDA receptor function.

Spatial discrimination reversal learning in weanling rats is impaired by striatal administration of an NMDA-receptor antagonist

“…The possible role of age differences might be related to the development of the NMDA-receptor system in the striatum of weanling and adult rats. NMDA receptor-binding density measured with autoradiography-labeled MK-801 in the neostriatum increases between P3 and P7 and again between P14 and P21, peaks on P28, and then decreases into adulthood (Colwell et al 1998). Increased binding density in weanlings may increase the potency of NMDA-receptor antagonists, and this might cause perseverative errors to increase at the expense of regressive errors at this age.…”

“…It may be possible that MK-801 is more potent in the weanling rat brain than in the adult rat brain-leading to age-related differences in performance characterized by more severe impairments (i.e., enhanced response perseveration) in young rats relative to older rats that typically display deficits in learning the new response pattern in the reversal phase (further considered in the Discussion) (Palencia and Ragozzino 2004). Of particular interest to the present study, NMDA-receptor binding increases across development in the neostriatum such that there is little function at P14, but the receptor binding peaks at P28 and then declines to adultlike levels by P60 (Colwell et al 1998). This decline in binding density across ontogeny may cause developmental changes in behavior during learning and memory tests following NMDAreceptor antagonism.…”

Dopamine Enhancement of NMDA Currents in Dissociated Medium-Sized Striatal Neurons: Role of D1 Receptors and DARPP-32

“…We purposely did not make direct comparisons because of the age differences. Although we used younger rats, our developmental studies indicate that by ϳ3 wk of age, responses to glutamate receptor agonists and dopaminergic modulation are relatively mature (Cepeda et al 1998a,b;Colwell et al 1998;Hurst et al 2001). However, in both species, D1-induced potentiation was observed and at least the effects of okadaic acid were similar, suggesting that comparable mechanisms may underlie the potentiation.…”

A Reconfiguration of CaV2 Ca2+ Channel Current and Its Dopaminergic D2 Modulation in Developing Neostriatal Neurons

“…This "replacement" of Ntype channels by P/Q-type channels has been observed in other CNS synapses, some of them inhibitory (Iwasaki and Takahashi 1998;Iwasaki et al 2000;Verderio et al 1995). However, this change seems to occur at later times in the synapses arising from spiny neurons (cf., Iwasaki et al 2000;see Tepper et al 1998), suggesting that these synapses undergo a somewhat late maturation (Colwell et al 1998;Tepper et al 1998) compared with other neurons. Because channel reconfiguration was observed at both the somatodendritic membrane and the synaptic terminals, the view that field stimulation in the globus pallidus preferentially activates striofugal axons from spiny neurons ) is therefore supported.…”