Host Corticostriatal Fibres Establish Synaptic Connections with Grafted Striatal Neurons in the Ibotenic Acid Lesioned Striatum

Abstract

The connections between host corticostriatal afferents and neurons in intrastriatal grafts of foetal striatal tissue have been studied with electron microscopic immunocytochemistry using Phaseolus vulgaris leucoagglutinin (PHA-L) as a label of the host corticostriatal fibres. Adult rats with unilateral ibotenic acid lesions of the head of the caudate putamen received foetal cell suspension grafts from E14-15 rat embryos into the lesioned striatal area. Ten months after transplantation, multiple iontophoretic injections of PHA-L were made into the host frontal cortex. These injections labelled large numbers of corticostriatal fibres which extended across the graft - host border to form a rich axonal network mainly in the peripheral portions of the grafts. At the ultrastructural level a total of 134 PHA-L-labelled terminals were identified to form asymmetric synaptic contacts with neurons within the grafts. Of these contacts, 83% were in contact with dendritic spines, 12% with dendritic shafts, and 5% with small shafts or spines. The synaptic contacts were similar to those identified in intact regions of the host striatum that were spared by the lesion. However, the synapses in the host striatum were almost exclusively in contact with spines (98%). These results demonstrate that the corticostriatal projection, which constitutes a major source of afferent control in the normal striatum, not only extends axons into the intrastriatal striatal grafts, but also establishes synaptic connections with the implanted neuronal elements.

Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey

“…The same dendrite receives symmetric synaptic contact (arrow) from another bouton, which in A seems to contain the BDHC reaction product indicating TH sory cortices in monkey terminate almost exclusively on the heads of dendritic spines. Previous ultrastructural data obtained in rat (Somogyi et al, 1981;Dube et al, 1988;Wictorin et al, 1989;Xu et al, 1989;Lapper and Bolam, 19921, cat (Kemp and Powell, 1971;Hassler et al, 1978;Frotscher et al, 1981) and monkey are consistent with the fact that the major postsynaptic targets of cortical afferents in the striatum are dendritic spines. Furthermore, the ultrastructural features and synaptic specializations of the anterogradely labelled cortical terminals observed in the present study are in keeping with those described in other species by means of anterograde labelling or anterograde degeneration methods (Kemp and Powell, 1971;Somogyi et al, 1981;Bouyer et al, 1984;Wictorin et al, 1989;.…”

“…Previous ultrastructural data obtained in rat (Somogyi et al, 1981;Dube et al, 1988;Wictorin et al, 1989;Xu et al, 1989;Lapper and Bolam, 19921, cat (Kemp and Powell, 1971;Hassler et al, 1978;Frotscher et al, 1981) and monkey are consistent with the fact that the major postsynaptic targets of cortical afferents in the striatum are dendritic spines. Furthermore, the ultrastructural features and synaptic specializations of the anterogradely labelled cortical terminals observed in the present study are in keeping with those described in other species by means of anterograde labelling or anterograde degeneration methods (Kemp and Powell, 1971;Somogyi et al, 1981;Bouyer et al, 1984;Wictorin et al, 1989;. Although the major targets of the cortical afferents observed in the present study were dendritic spines, the possibility that dendritic shafts receive inputs from the primary motor and somatosensory cortices is not ruled out since a small proportion (8%) of striatal elements that formed synapses with the cortical terminals could not be identified.…”

“…It is therefore possible that some of these unidentifiable targets were segments of dendritic shafts. In fact, axodendritic synapses formed by cortical boutons were observed in previous studies (Kemp and Powell, 1971;Frotscher et al, 1981;Wictorin et al, 1989;Xu et al, 1989;. Although they represented a small proportion of the total population of synapses formed by cortical boutons in the striatum, the axodendritic synaptic contacts may still be of functional importance since some of them are likely to be a source of direct cortical i n m t to the asDinv striatal interneuimmunoreactivity.…”

Morphological and cellular changes within embryonic striatal grafts associated with enriched environment and involuntary exercise

“…The finding that the spine density of grafted neurons is affected by experimental conditions strongly suggests that, following transplantation, these cells can still proceed with the multitude of molecular mechanisms required for the formation, elimination, motility and stability of dendritic spines (Lippman & Dunaevsky, 2005; Tada & Sheng, 2005). The presence of the spines on the grafted neurons indirectly demonstrates that they receive excitatory inputs, which previous studies suggest to be glutamatergic afferents from the cortex (Wictorin et al ., 1989b), and that the grafts contain AMPA and N ‐methyl‐ d ‐aspartate (NMDA) receptors on which hinge many of the downstream signals inducing morphological changes (Tada & Sheng, 2005).…”

Review: The fate of cell grafts for the treatment of Huntington's disease: the post‐mortem evidence

“…There is currently no disease-modifying treatment for HD [31]. Experimental approaches using foetal striatal transplants have thus been initiated based on (a) the early success with similar strategies in the treatment of PD [32,33]; (b) the favourable behavioural and anatomical results from preclinical animal studies in models of HD [34][35][36][37][38][39][40]; and (c) the lack of adequate treatment for HD, which is invariably fatal [24,31]. As of now, seven independent pilot clinical trials have been conducted worldwide (Table 1) with the purpose of assessing the feasibility, safety and tolerability of this procedure in HD patients [18,19,41].…”