Synaptic Plasticity in the Rat Neostriatum after Unilateral 6-Hydroxydopamine Lesion of the Nigrostriatal Dopaminergic Pathway
Parkinson’s disease is characterised by the loss of dopaminergic neurons in the substantia nigra, pars compacta which normally provide dopaminergic input to the caudate nucleus and putamen (neostriatum). One of the well used ‘animal models’ of the disorder involves unilateral destruction of the dopaminergic pathway by injecting the toxin, 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle where it is taken up selectively by dopaminergic axons resulting in the death of all parts of the neuron (Ungerstedt and Arbuthnott, 1970). Several morphological changes have been described in the neostriatum after this manipulation including a 12–19% decrease in the density of dendritic spines on the medium sized spiny neurons (Ingham et al., 1993; Ingham et al., 1989). Sixty percent of dopaminergic synaptic boutons identified by tyrosine hydroxylase immunoreactivity contact the dendritic spines of these neurons but the synapses are small, symmetric and contact the spine necks (Freund et al., 1984). The main synaptic input to dendritic spines is from the cortex and thalamus, it is thought to be excitatory and the synaptic contacts are large, asymmetric and are often complex in shape (Somogyi et al., 1981; Kemp and Powell, 1971). The decrease in spine density which occurs after removal of the dopaminergic input raises the question of what happens to the excitatory input onto the heads of spines. These synapses may move to an alternative postsynaptic target or disappear after the 6-OHDA lesion. The vast majority of asymmetric synapses in the neostriatum are axo-spinous and so this question can be addressed by examining the numerical density of asymmetric synaptic contacts in the structure after unilateral 6-OHDA lesions.
KeywordsDopamine Tyrosine Citrate Dehydration Neurol
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