Synapse replacement in the striatum of the adult rat following unilateral cortex ablation

Abstract

Defining the selective pattern of synapse replacement that occurs in different areas of the damaged brain is essential for predicting the limits of functional compensation that can be achieved after various types of brain injury. Here we describe the time course of dendritic reorganization, spine loss and recovery, and synapse replacement in the striatum following a unilateral cortex ablation. We found that the time course for the transient loss and recovery of dendritic spines on medium spiny I (MSI) neurons, the primary postsynaptic target for corticostriatal axons, paralleled the time course for the removal of degenerating axon terminals from the neuropil and the formation of new synapses on MSI neurons. Reinnervation of the deafferented striatum occurred chiefly by axon terminals that formed asymmetric synapses with dendritic spines of MSI neurons, and the mean density of asymmetric synapses recovered to 86% of the sham-operated rat value by 30 days postlesion. In addition, the synaptic circuitry of the reconstructed striatum was characterized by an increase in the number of multiple synaptic boutons (MSBs), i.e., presynaptic axon terminals that make contact with more than one dendritic spine. Whether the postsynaptic contacts of MSBs are formed with the dendritic spines of the same or a different parent dendrite in the striatum is unknown. Nevertheless, these data suggest that the formation of MSBs is an essential part of the compensatory response to the loss of input from the ipsilateral cortex following the aspiration lesion and may serve to modulate activity-dependent adaptive changes in the reconstructed striatum that can lead to functional recovery.

Glial overexpression of heme oxygenase-1: a histochemical marker for early stages of striatal damage

“…1 or 3 weeks postlesion). After intrastriatal injection of high doses of excitotoxins or after surgical lesioning, HO-1-ir cells were still observed 3 weeks post-lesion, which is consistent with a still active striatal lesion and glial reaction (Akiyama and McGeer, 1989;Marty et al, 1991;Dusart et al, 1991;Rodrigues et al, 2001;McNeil et al, 2003). Furthermore, we observed HO-1-ir in glial cells but we did not find any consistent HO-1 overexpression in striatal neurons.…”

“…Finally, HO-1 astrocytes observed 1 or 3 weeks after surgical corticostriatal deafferentation may also be related to phagocytic activity. A recent ultrastructural study (McNeil et al, 2003) on the synaptic changes observed in the striatum after unilateral cortical ablation has shown that changes in degenerating corticostriatal terminals occur more slowly than reported for other regions of the brain. Maximal terminal degeneration occurred at 10 days postlesion, and there are still degenerating terminals 30 days post-lesion.…”

“…In the past, conflicting views have been expressed regarding the role of astrocytes in phagocytosis. However, more recent studies have demonstrated not only the unequivocal involvement of astrocytes in the phagocytic activity, but also that reactive astrocytes are the major phagocytic cells responsible for the removal of degenerating presynaptic terminals from the neuropil, and that they have multifunctional roles in reactive synaptogenesis (Matthews et al, 1976;McWilliams and Lynch, 1979;Al-Ali and Al-Hussain, 1996;McNeil et al, 2003). HO-1 may breakdown hemecontaining proteins in engulfed material from dead neurons or axons to yield bilirubin and iron.…”

Differential striatal spine pathology in Parkinson’s disease and cocaine addiction: A key role of dopamine?

“…In vitro and in vivo data in rats, indeed, demonstrated that decortication prevents the loss of striatal spines induced by dopamine denervation, thereby suggesting that glutamate is another key determining factor of this pathology (Cheng et al, 1997; McNeill et al, 2003; Deutch et al, 2007; Neely et al, 2007; Garcia et al, 2010). As discussed below, functional interactions between regulating elements of convergent glutamatergic and dopaminergic synapses upon striatal spines, and their impact on the control of intracellular calcium levels, may be critical factors that underlie these functional interactions between glutamatergic and dopaminergic systems to regulate spine pruning and morphology in PD.…”

Use it and/or lose it—experience effects on brain remodeling across time after stroke

“…Synapse densities around an infarct decline and then recover over time to varying degrees depending on proximity to the infarct core (Brown et al, 2008; Sigler and Murphy, 2010). Remaining projections to denervated regions sprout collateral axons and form new synapses (Cotman and Anderson, 1988; McNeill et al, 2003; Dancause et al, 2005). The axons that most prominently contribute to reinnervation tend to be the most abundant (Raisman and Field, 1990) and the most active (in firing) of the surviving projections (Carmichael and Chesselet, 2002; Carmichael, 2003; Cesa and Strata, 2005; Brus-Ramer et al, 2007).…”