Quantitative electron microscopic evidence for reinnervation in the adult rat interpeduncular nucleus after lesions of the fasciculus retroflexus

Abstract

The method of electron dense degeneration has been used to make a quantitative study of the projection from the habenula through the fasciculus retroflexus (FR) to the interpeduncular nucleus (IPN) in the rat. The IPN si a midline structure onto which the right and left fasciculi converge. In the rostral part of the IPN the fascicular axons from each side form synapses throughout the mediolateral extent of the ventral two-thirs of the nucleus. In the caudal part of the IPN the fascicular axons from each side terminate to an equal extent in two discrete, parasagittal zones, situated one on side in the mid-mediolateral extent of the IPN. These zones contain clusters of neurons located along the course of a characteristic row of arterioles and venules penetrating the IPN from its ventral surface. In both rostral and caudal parts of the IPN the fascicular axons form single synaptic contaerpeduncular neurons, but caudally, in the two parasagittal zones they also form crest synapses. Crest synapses are only found in this part of the IPN. In crest synapses two presynaptic terminals form markedly asymmetrical contacts with the parallel opposing sides of an attenuated dendritic appendage (the crest). After unilateral fascicular lesions only one member of a pair of axon terminals contacting a crest degenerates. After bilateral fascicular lesions, however, there are many instances in which both members of a crest pair degenerate. This indicates that the axon terminals from the right and left fasciculi are segregated at the level of the crests, in such a way that one terminal comes from the right fasciculus and one from the left. At longer survivals after unilateral or bilateral fasciculus lesions the degeneration is completely removed, but crest synapses are still present, indicating that the presence of fascicular axons is not necessary for the maintenan ce of crests in the IPN. To investigate the effects of chronic deafferentation, the left fasciculus was destroyed and, after a survival of at least six weeks (sufficient for all degeneration to be removed) the right fasciculus was destroyed one day before killing. Under these conditions there are many crests in which both axon terminals show degeneration. The proportion of such doubly degenerating crest synapses is similar to that found after acute (1 day) bilateral lesions, indicating that axons from the right fasciculus have reinnervated sites formerly occupied by the left fasciculus. We conclude that during normal development there is some constraint which prevents both sides of a crest being innervated by axons from the fasciculus of the same side of the brain, but that this constraint is not effective after unilateral fascicular lesions in the adult.

Neuroplasticity and the Developing Brain: Implications for Therapy

“…Two months after crest synapses are deafferented by a unilateral MH lesion in the normal adult, 66% or more of all those remaining are formed by two MH axons which are necessarily from the same unlesioned MH [35]. This is an impressive degree of reactive reinnerva tion compared to other brain regions.…”

“…There is evidence of local pro tein synthesis at these sites during development (unpub lished observations). In the normal adult, one of the cholinergic MH endings at 90% of crest synapses is from a left MH neuron, while the other is from the right MH [32,35]. This is true in both the left and right inter mediate subnuclei.…”

Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus

“…The projections to the IPN are characterized by robust lesion induced plasticity (Lenn, 1978;Lenn et al, 1979;Murray et al, 1979;Artymyshyn and Murray 1985;Barr et al, 1987;Battisti et al, 1987Battisti et al, , 1989Eckenrode et al, 1987), and this has been particularly well described for the habenular projections. Unilateral FR lesions in rats evoke partial replacement of SP, and this sprouting is similar whether the lesion is made in neonates or adults (Artymyshyn and Murray, 1985;Barr et al, 1987).…”

“…The FRs form two heavily myelinated bundles of axons, readily recognized as they exit from the ventral surface of the medial habenula, which course ventrally and caudally to enter the rostra1 pole of the IPN. Lesions placed in the caudal diencephalon destroy the FRs without damaging the IPN (see Murray et al, 1979Murray et al, , 1988.…”

“…The habenular cholinergic projection does have the peculiar feature of innervating the system of crest synapses that densely populate the intermediate subnuclei. These synapses are complex structures, Most studies in which fetal transplants have been used to reinin which one terminal arises from cells in the left habenula and nervate denervated structures have emphasized the restoration the other terminal arises from cells in the right habenula (Lenn, of normal patterns of projections and therefore, by extension, 1976;Murray et al, 1979;Lenn et al, 1983). This left-right of normal innervation (Foster et al, 1985(Foster et al, , 1988aFreund et organization develops postnatally and indicates an additional al., 1985; Zhou et al, 1985;Gage and Bjorklund, 1986; Gibbs constraint on the formation of synaptic complexes involving et al., 1986;Anderson et al, 1988;Clarke et al, 1990; Radel habenular neurons that may not operate in the formation of et al, 1990).…”