The process of reinnervation in the dentate gyrus of adult rats: An ultrastructural study of changes in presynaptic terminals as a result of sprouting

Abstract

The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway after they had sprouted to reinnervate the dentate gyrus following the destruction of the normal ipsilateral temporodentate pathway. The synapses of the sprouted crossed temporodentate pathway were identified at the EM level by using autoradiographic techniques and by evaluating the degeneration of the pathway following secondary lesions. Both EM autoradiography and EM degeneration revealed that the terminals of the sprouted crossed temporodentate pathway formed asymmetric synapses on spines; individual terminals appeared to make more synaptic contacts per terminal (multiple synapses) than in the case of the normal crossed pathway. In the two lesioned animals exhibiting the best labeling, labeled terminals made an average of 3.0 ± 2.2 and 2.0 ± 1.3 contacts per terminal. In contrast, labeled terminals in normal animals exhibited only one contact per terminal. The terminals of the sprouted pathway were also larger than those of the normal crossed pathway. The synapses of the crossed temporodentate pathway that degenerated after a secondary lesion of the entorhinal cortex exhibited both electron‐lucent and electron‐dense forms of degeneration at 2 days postlesion. In two animals that were quantitatively analyzed, the density of degenerating synaptic terminals was 281 and 218/10,000 μm2 in the terminal field of the sprouted crossed pathway. These values are much higher than in normal animals, where the density of degenerating synaptic terminals was only 2.12/10,000 μm2 at 2 days postlesion. Because degenerating terminals were evident at 2 days postlesion, the sprouted crossed pathway does not appear to exhibit the very rapid degeneration that is characteristic of the normal crossed pathway. We conclude that sprouting in this pathway involves terminal proliferation (an increase in the number of presynaptic elements), and terminal hypertrophy (an increase in the size of presynaptic terminals, together with an increase in the number of synaptic contacts formed by individual terminals).

Associative Learning Elicits the Formation of Multiple-Synapse Boutons

“…Interestingly, this morphological alteration is not unique to behavioral learning and related phenomena such as hippocampal LTP (Toni et al, 1999) and an exposure to enriched environments (Jones et al, 1997). The incidence of MSBs has been reported to increase in various regions of the CNS under conditions that induce plasticity: in the rat dentate gyrus for boutons of the crossed temporodentate pathway after lesions of the ipsilateral entorhinal cortex (Steward et al, 1988); in the rat hypothalamus as a consequence of lactation, dehydration, or partial deafferentation (for review, see Hatton, 1990); in the cat visual cortex after monocular visual deprivation in the case of boutons on geniculocortical axons that were driven from the nondeprived eye (Friedlander et al, 1991); in the CA1 stratum radiatum of adult female rats after estradiol treatment (Woolley et al, 1996); in the rat phrenic nucleus as a result of an ipsilateral C2 spinal cord hemisection (Tai et al, 1997) or a cold block of ipsilateral bulbospinal respiratory afferents (CastroMoure and Goshgarian, 1997); in the rat motor cortex after lesions of the contralateral sensorimotor cortex (Jones, 1999); in the rat CA1 stratum radiatum after maintenance of living hippocampal slices in vitro (Kirov et al, 1999); and in the rat striatum after an ablation of the ipsilateral frontal cortex (Meshul et al, 2000). These observations indicate that the formation of MSBs may represent a general form of structural synaptic plasticity.…”

MT5-MMP, ADAM-10, and N-Cadherin Act in Concert To Facilitate Synapse Reorganization after Traumatic Brain Injury

“…Under adaptive conditions, synaptic reorganization occurs in serial postinjury phases: acute degradation of injured axons (1-5 days); subsequent regeneration of new synapses (6-15 days); and synaptic maturation (15-30 days + ; Steward and Vinsant, 1983). The unilateral entorhinal cortex lesion (UEC) is a wellestablished model of hippocampal synaptic plasticity, resulting in adaptive reorganization (Steward et al, 1988). By contrast, the combination of moderate central fluid percussion TBI with bilateral entorhinal cortex lesion (TBI + BEC) leads to maladaptive synaptic plasticity, with persistent structural, functional, and behavioral deficits (Phillips and Reeves, 2001;Phillips et al, 1994).…”

Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling mouse hippocampus after entorhinal cortex lesion and liver-X receptor agonist treatment

“…This synaptic loss is transient. Within few weeks, more than 80% of entorhinal synapses are replaced by fiber connections that originate from cholinergic septal neurons, glutamatergic commissural-associational cells of the CA3/hilar areas and to a lesser extent (~5%), from the contralateral entorhinal cortex (Matthews et al, 1976;Phinney et al, 2004;Poirier et al, 1993;Steward et al, 1988). Fig.…”