Effects Of BDNF On GABAergic Transmission In The Projection Neurons Of Cerebellar Interpositus Nucleus And The Underlying Receptor Mechanism

Brain-derived neurotrophic factor (BDNF) is the second found member of the neurotrophic family of growth factors and was first purified by Barde et al. from pig brain in1982. BDNF has a widespread distribution in the central and peripheral nervous systems, including subcortical motor structures, such as the cerebellum, basal ganglia, brainstem vestibular nuclei and even spinal cord, suggesting BDNF may play a role in the regulation of motor control. However, the direct actions of BDNF on the neuronal electrical activity in central motor structures and their underlying mechanisms are still largely unknown to date.The cerebellum, as the biggest subcortical motor structure, plays an important function in motor control. It is involved in the regulation of body balance, muscle tone, voluntary movement coordination and motor learning through rich afferent and efferent fibers with cerebral cortex, brainstem and spinal cord. The cerebellar nuclei, receiving and integrating the information from cerebellar cortical GABAergic Purkinje cells, mossy fibers and climbing fibers, are the final output node of the cerebellum (excluding the flocculonodular lobe). In the cerebellar nuclei, the interpositus nucleus, as one of the final output of the spinocerebellum, responsible for regulating ongoing movements, plays an important function in motor behaviors and motor learning. Therefore, by using quantitative RT-PCR, immunocytochemistry and whole-cell patch clamp recordings, the present study was designed to investigate the effects of BDNF on electrical activity and GABAnergic transmission in the projection neurons of cerebellar interpositus nucleus and the underlying receptor mechanism.The results are as follows:(i) BDNF and its receptors TrkB had an extensive expression in the cerebellar cortex and interpositus nucleus;(ii) BDNF did not produce a direct excitatory or inhibitory effect on the projection neurons of cerebellar interpositus nucleus;(iii) BDNF dose-dependently increased the muscimol (selevtive agonist for GABAA receptor)-mimicked GABAergic transmission in the projection neurons of cerebellar interpositus nucleus;(iv) the enhancement of BDNF on the GABAergic transmission in the projection neurons of cerebellar interpositus nucleus was a direct postsynaptic effect;(v) the BDNF-induced enhancement of the GABAergic transmission was mediated by the activation of TrkB receptors.These results suggest that BDNF is directly involved in the regulation of GABAergic transmission in the projection neurons of cerebellar interpositus nucleus through postsynaptic TrkB receptors. Considering that the GABAergic synaptic transmission of projection neurons in the cerebellar interpositus nucleus mainly comes from Purkinje cells, the unique output of cerebellar cortex, we speculate that BDNF may play an important role in the information integration in the cerebellar nuclei and participate in motor behaviors and motor learning via the cerebellar circuitry.