Rho GTPase-dependent plasticity of dendritic spines in the adult brain

Abstract

Brain activity is associated with structural changes in the neural connections. However, in vivo imaging of the outer cortical layers has shown that dendritic spines, on which most excitatory synapses insist, are predominantly stable in adulthood. Changes in dendritic spines are governed by small GTPases of the Rho family through modulation of the actin cytoskeleton. Yet, while there are abundant data about this functional effect of Rho GTPases in vitro, there is limited evidence that Rho GTPase signaling in the brain is associated with changes in neuronal morphology. In the present work, both chronic in vivo two-photon imaging and Golgi staining reveal that the activation of Rho GTPases in the adult mouse brain is associated with little change of dendritic spines in the apical dendrites of primary visual cortex pyramidal neurons. On the contrary, considerable increase in spine density is observed (i) in the basal dendrites of the same neurons (ii) in both basal and apical dendrites of the hippocampal CA1 pyramidal cells. While confirming that Rho GTPase-dependent increase in spine density can be substantial, the study indicates region and dendrite selectivity with relative stability of superficial cortical circuits.

APC/C Cdh1 -Rock2 pathway controls dendritic integrity and memory

“…The RhoA-Rock2 pathway mediates remodeling of dendritic spine morphology and density downstream of glutamate receptor activation (35,36). Therefore, the APC/C Cdh1 -Rock2 signaling pathway is consistent with the previously described effect of APC/C Cdh1 on synaptic plasticity, including long-term potentiation, mGluR-dependent long-term depression, and homeostatic synaptic plasticity (10,(37)(38)(39).…”

Bacterial Toxins and Targeted Brain Therapy: New Insights from Cytotoxic Necrotizing Factor 1 (CNF1)

“…By activating Rho GTPases, CNF1 induces a remarkable reorganization of the actin cytoskeleton [ 3 ]. This capability, previously observed in epithelial cells [ 37 , 38 ], has also been demonstrated in neurons [ 39 , 40 , 41 , 42 ]. Indeed, intracerebral injection of CNF1 in adult rodents leads to a long-lasting activation of Rac1 that results in marked neural structural remodeling.…”

“…Accordingly, both chronic in vivo two-photon imaging and Golgi staining reveal that intracerebroventricular injection of CNF1 increases spine density in visual and hippocampal neurons, albeit with region-specific features. Indeed, structural changes are evident in both apical and basal dendrites in hippocampal pyramidal neurons, while in primary visual cortex they are restricted to basal dendrites [ 41 ]. Results from in vitro experiments suggest that these morphological changes are probably mediated by astrocytes, as direct administration of CNF1 to neuronal cultures has a harmful effect on neuronal maturation, while hippocampal neurons grown in CNF1-treated astrocytes show an increased development of neurites [ 42 ].…”

“…CNF1-induced neuronal remodeling has important functional consequences. In vitro experiments have shown that CNF1 enhances glutamatergic neurotransmission and long-term potentiation in hippocampal neurons [ 39 , 41 ]. Noteworthy, we demonstrated that in vivo stimulation of structural rearrangements by CNF1 is able to reinstate functional plasticity in the adult rat visual cortex.…”

Therapeutic effects of the Rho GTPase modulator CNF1 in a model of Parkinson’s disease

“…Therefore, the trophic effect of CNF1 was not selective for DA cells. It is worth mentioning that CNF1 also induces hypertrophy of neural processes and the growth of spine-like formations in cortical and hippocampal neurons from wild type mice (Diana et al, 2007;Martino et al, 2013). Frequent growth cones were observed in CNF1-treated neurons by phalloidin staining (Figure 2 l).…”