Enhanced cortical and hippocampal neuronal excitability in mice deficient in the extracellular matrix glycoprotein tenascin-R

Hippocampal Metaplasticity Induced by Deficiency in the Extracellular Matrix Glycoprotein Tenascin-R

“…In addition, ultrastructural analysis of inhibitory perisomatic terminals on pyramidal cells in the CA1 regions in TNRϪ/Ϫ mice revealed a reduction in the density of perisomatic synapses and abnormalities in their architecture, including a reduction in the size of active zones and distribution of synaptic vesicles (Nikonenko et al, 2003). Also, TNRϪ/Ϫ mice showed elevated levels of AMPA receptor-mediated excitatory synaptic transmission after the second week of postnatal development (Saghatelyan et al, 2001) (present study) and increased amplitudes of auditory evoked potentials and hippocampal ␥-oscillations in freely moving adult mice (Gurevicius et al, 2004). The latter data, together with our ultrastructural observations on elevated density of perforated synapses in the CA1 stratum radiatum of TNRϪ/Ϫ mice (O. Nikonenko, unpublished observations), support the view that excitatory transmission is elevated in this mutant not only in vitro, but also in vivo.…”

Chondroitin Sulfate Proteoglycan Tenascin-R Regulates Glutamate Uptake by Adult Brain Astrocytes

“…The molecular mechanisms underlying the scaffolding activity include protein-protein interactions between TNR and lecticans (40 -43). In addition to these protein-protein interactions, TNR is involved in regulating the action potential conduction of neurons (39) and in neuronal excitability (44,45). Those studies primarily focused on neuronal functions using TNRknock-out mice, although the present findings further implicate TNR in glial functions, as it was found in a subset of astrocytes and regulated expression levels of the glutamate transporter GLAST, which takes up glutamate from synaptic clefts and thereby modulates glutamatergic neurotransmission (46 -48).…”

“…These homeostatic mechanisms are also important in the case of neuronal injury and ischemia, because excess glutamate harms neurons in such pathological conditions (49). In this regard, part of the enhanced excitability of neurons in TNR-knock-out mice (44,45,50) may be attributed to a reduction of GLAST expression levels. Consistent with this possibility, TNR is up-regulated in astrogliosis (51,52).…”

Tenascin-R Restricts Posttraumatic Remodeling of Motoneuron Innervation and Functional Recovery after Spinal Cord Injury in Adult Mice

“…Reduced inhibition and enhanced excitatory transmission have been well documented for the hippocampus of TNR Ϫ/Ϫ mice (Saghatelyan et al, 2001). The functional consequences of these abnormalities are impairments in long-term potentiation in the hippocampus and cortical and hippocampal neuronal hyperexcitability (Saghatelyan et al, 2000(Saghatelyan et al, , 2001Brenneke et al, 2004;Gurevicius et al, 2004). The abnormalities found in the intact spinal cord may contribute to motor impairments of TNR Ϫ/Ϫ mice that become apparent under demanding conditions, such as rotarod, pole, and wirehanging tests (Freitag et al, 2003), but are not detectable in less stressful and challenging tests as those used here for analysis of motor functions.…”