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Neuroscience. 2012 Oct 11;222:215-27. doi: 10.1016/j.neuroscience.2012.07.005. Epub 2012 Jul 13.

Impaired transmission at corticothalamic excitatory inputs and intrathalamic GABAergic synapses in the ventrobasal thalamus of heterozygous BDNF knockout mice.

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1
Institut für Physiologie, Medizinische Fakultät, Otto-von-Guericke-Universität, Leipziger Str. 44, D-39120 Magdeburg, Germany.

Abstract

Beside its role in development and maturation of synapses, brain-derived neurotrophic factor (BDNF) is suggested to play a critical role in modulation and plasticity of glutamatergic as well as GABAergic synaptic transmission. Here, we used heterozygous BDNF knockout (BDNF(+/-)) mice, which chronically lack approximately 50% of BDNF of wildtype (WT) animals, to investigate the role of BDNF in regulating synaptic transmission in the ventrobasal complex (VB) of the thalamus. Excitatory transmission was characterized at glutamatergic synapses onto relay (TC) neurons of the VB and intrathalamic inhibitory transmission was characterized at GABAergic synapses between neurons of the reticular thalamic nucleus (RTN) and TC neurons. Reduced expression of BDNF in BDNF(+/-) mice did not affect intrinsic membrane properties of TC neurons. Recordings in TC neurons, however, revealed a strong reduction in the frequency of miniature excitatory postsynaptic currents (mEPSCs) in BDNF(+/-) mice, as compared to WT littermates, whereas mEPSC amplitudes were not significantly different between genotypes. A mainly presynaptic impairment of corticothalamic excitatory synapses in BDNF(+/-) mice was also indicated by a decreased paired-pulse ratio and faster synaptic fatigue upon prolonged repetitive stimulation at 40 Hz. For miniature inhibitory postsynaptic currents (mIPSCs) recorded in TC neurons, both, frequency and amplitude showed a significant reduction in knock-out animals, concurrent with a prolonged decay time constant, whereas paired-pulse depression and synaptic fatigue of inhibitory synapses were not significantly different between WT and BDNF(+/-) mice. Spontaneous IPSCs (sIPSCs) recorded in VB neurons of BDNF(+/-) animals showed a significantly reduced frequency. However, the glutamatergic drive onto RTN neurons, as revealed by the percentage reduction in frequency of sIPSCs after application of AMPA and NMDA receptor blockers, was not significantly different. Together, the present findings suggest that a chronically reduced level of BDNF to ∼50% of WT levels in heterozygous knock-out animals, strongly attenuates glutamatergic and GABAergic synaptic transmission in thalamic circuits. We hypothesize that this impairment of excitatory and inhibitory transmission may have profound consequences for the generation of rhythmical activity in the thalamocortical network.

[Indexed for MEDLINE]

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