~ ) Pergamon Neuroscience Vol. 84. No. 4, pp. 1163 1175. 1998 Copyright ,~': 1998IBRO. Publishedby ElsevierScience Ltd Printed in Great Britain. All rights reserved PII: S0306-4522(97)00583-6 0306M522/98 $19.00+0.00 POSTNATAL DEVELOPMENT OF EXCITATORY SYNAPTIC INPUT TO THE RAT NEOSTRIATUM: AN ELECTRON MICROSCOPIC STUDY N. A. SHARPE and J. M. TEPPER* Aidekman Research Center, Center for Molecular and Behavioral Neuroscience and Program In Cellular and Molecular Biodynamics, Rutgers, The State University of New Jersey, Newark, New Jersey, U.S.A. Abstract The distribution and density of asymmetric synapses including biocytin-labelled corticostriatal synapses of the rat neostriatum were examined at postnatal day 10 (P10), P15, P21 and in adults. The density of asymmetric synapses in the adult neostriatum (28.0 synapses/100 lain 2) was significantly greater than that in neonates at PI5 (14.4 synapses/100 gm2) and PI0 (11.5 synapses/100 gm2), but not at P21 (24.2 + 1.5 synapses/100 p_m2).The increased density of asymmetric synapses in the adult neostriatum was due primarily to an increase in the number of axospinous synapses. The density of axospinous synapses was greatest in adults (22.3 synapses/100 jam 2) and significantly less at P21 (15.3 synapses/100 p_m2), PI5 (5.9 synapses/100 gin2), and P10 (2.0 synapses/100 gm2). The density of axodendritic synapses, however, remained similar at all ages (adult, 3.94-1.1 synapses/100gm2; P21, 6.0+ 1.2 synapses/100gm2; P151 5.7 ± 0.8 synapses/100 gm2 or P10, 7.2 4- 1.3 synapses/100 gm2). Iontophoretic injection of biocytin into the lateral frontal agranular cortex produced labelling of corticostriatal afferents which formed asymmetric synapses in the neostriatum. The distribution of termination sites of biocytin-labelled corticostriatal boutons showed a pattern of development similar to the unlabelled asymmetric synapses. The present study shows that the increase in the overall number of asymmetric synapses over the first three postnatal weeks can be attributed to an increase in the density of asymmetric axospinous synapses. During the same period little change is noted in the number or density of asymmetric axodendritic synapses. These changes in excitatory synaptic input to medium spiny neurons may explain some of the previously described electrophysiological differences noted between the neonatal and adult neostriatum. () 1998 IBRO. Published by Elsevier Science Ltd. KCv words: basal ganglia, biocytin, dendritic spine, development, neonatal, corticostriatal. The majority of afferents to the basal ganglia terminate in the neostriatum. Various areas of the neocortex, including the prefrontal, motor, somato- sensory and visual areas, along with the thalamus, form the primary excitatory inputs to the dorsal neostriatum. 15"17'23b'2~'39'41 The majority of cortical afferents in the adult neostriatum form asymmetric synapses onto spine heads. 17-25,26,2s.41 Thalamic afferents terminate onto both spine heads and dendritic shafts. 17,25.26,38 Both of these afferents are believed to be excitatory and use glutamate or another excitatory amino acid as their neuro- transmitter. 6 The anatomy and electrophysiology of cortical input to the neostriatum of the adult rat have been studied extensively. 6,1°,17,24.37,46,51 The morpho- logical and electrophysiological properties of the medium spiny neuron, the principal neuron of the neostriatum, have also been well characterized in the adult rat. 5'16-]~'53 Information is available on the postnatal development of feline and primate *To whom correspondence should be addressed. Abbreviations: DAB, 3,3'-diaminobenzidine; EPSP, excita- tory postsynaptic potential; IPSP, inhibitory postsynaptic potential; P, postnatal day; PB, phosphate buffer. neostriatum. 1,7,12,15,21,30 However,only limited infor- mation is available on the postnatal development of the corticostriatal pathway 19 and other afferents to the rat neostriatal medium spiny neuron. 22,4345 Light microscopic studies have shown that the dendritic morphology of the adult and neonatal medium spiny neuron differ significantly in felines, primates and rats with the density of dendritic spines increasing over development. 1,12-21.43 45 In the adult rat, the medium spiny neuron is highly spiny, with a maximum spine density of 4~6 spines/~tm of dendrite measured approximately 80 gm from the soma. 52 In the early neonatal rat, the medium spiny neuron is almost totally aspiny, and possesses thin and varicose dendrites. 45 The greatest increase in spine density occurs during the third postnatal week, correspond- ing to the time when the majority of the cortical and thalamic afferents innervate the neostriatum. 19 This timing also corresponds to the period when the most significant electrophysiological changes are noted.34"43"44 Characterization of corticostriatal and other excitatory synaptic inputs to the medium spiny neuron over postnatal development may provide a basis for explaining functional differences between 1163