Abstract
The cortico-collicular pathway is a bilateral excitatory projection from the cortex to the inferior colliculus (IC). It is asymmetric and predominantly ipsilateral. Using microarrays and RT-qPCR we analyzed changes in gene expression in the IC after unilateral lesions of the auditory cortex, comparing the ICs ipsi- and contralateral to the lesioned side. At 15 days after surgery there were mainly changes in gene expression in the IC ipsilateral to the lesion. Regulation primarily involved inflammatory cascade genes, suggesting a direct effect of degeneration rather than a neuronal plastic reorganization. Ninety days after the cortical lesion the ipsilateral IC showed a significant up-regulation of genes involved in apoptosis and axonal regeneration combined with a down-regulation of genes involved in neurotransmission, synaptic growth, and gap junction assembly. In contrast, the contralateral IC at 90 days post-lesion showed an up-regulation in genes primarily related to neurotransmission, cell proliferation, and synaptic growth. There was also a down-regulation in autophagy and neuroprotection genes. These findings suggest that the reorganization in the IC after descending pathway deafferentation is a long-term process involving extensive changes in gene expression regulation. Regulated genes are involved in many different neuronal functions, and the number and gene rearrangement profile seems to depend on the density of loss of the auditory cortical inputs.
Highlights
The inferior colliculus (IC) is an obligatory relay station for almost all ascending and descending auditory projections and it is a key nucleus for excitatory and inhibitory auditory input convergence (Malmierca and Merchán, 2004)
We detected changes in genes involved in myelin organization and regulation as Peripheral myelin protein 22 (Pmp22) and Developmentally regulated protein TPO1 (Tpo1), Myelin-associated glycoprotein (Mag ), and Oligodendrocyte-myelin glycoprotein (Omg ). We found both types of regulation in genes involved in sprouting [dopamine receptor D1 interacting protein (Drd1ip), Sprouty homolog 3 (Spry-3), and Rho-associated coiled-coil containing protein kinase 1 (Rock1)], in synaptic plasticity [Amyloid beta (A4) precursor protein (App), Neuronal pentraxin 2 (Nptx2) and Calcium/calmodulin-dependent protein kinase II, β Camk2b] and in postsynaptic density reorganization (p55, and Tubulins γ2, α1A, and β2C)
Auditory cortical ablation affects a large number of genes simultaneously; at 15 days post-lesion we found 52 genes (33 in the ipsilateral side and 19 in the contralateral side) whose expression changes
Summary
The inferior colliculus (IC) is an obligatory relay station for almost all ascending and descending auditory projections and it is a key nucleus for excitatory and inhibitory auditory input convergence (Malmierca and Merchán, 2004). The descending cortico-collicular projection acts as a filter for neuronal responses (Sun et al, 2007). It participates in a positive feedback loop which, in combination with lateral inhibition, sharpens, and adjusts the tuning of neurons in the auditory pathway (Zhang et al, 1997; Jen and Zhang, 1999). The descending auditory corticofugal projection is glutamatergic and excitatory (Feliciano and Potashner, 1995). It is bilateral, but is denser on the ipsilateral side (Saldana et al, 1996; Bajo et al, 2007). Corticofugal deactivation results in unbalanced excitatory/inhibitory IC afferent projections, which induce alterations in the amplitude and latencies of IC neuronal responses (Nwabueze-Ogbo et al, 2002; Popelar et al, 2003), indicating that this projection affects directly the activity of IC neurons
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