Modulatory projections from brainstem nuclei and intrinsic thalamic interneurons play a significant role in modifying sensory information as it is relayed from the thalamus to the cortex. In the lateral geniculate nucleus (LGN), neurotransmitters released from these modulatory inputs can affect the intrinsic conductances of thalamocortical relay neurons, thus altering their firing properties. Here, we show that in addition to postsynaptic effects, neuromodulators such as serotonin (5-HT) and

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... A can act presynaptically to regulate neurotransmitter release at the synapse between retinal ganglion cells (RGCs) and relay neurons in the LGN, the retinogeniculate synapse. Activation of 5HT 1 and GABA B receptors significantly decreased EPSC amplitude. This inhibition was accompanied by a decrease in the extent of paired-pulse depression, suggesting that it is presynaptic in origin. In addition, fluorometric calcium measurements from retinal axon terminals labeled with Calcium Green-1 dextran revealed that 5HT 1 and GABA B receptor agonists decreased presynaptic calcium influx. Taken together, our data indicate that serotonin and GABA can act presynaptically to decrease calcium influx at the retinogeniculate synapse and modify transmission of visual information in the LGN.