The basal forebrain (BF) receives afferents from brain stem ascending pathways, which has been implicated first by Moruzzi and Magoun (Moruzzi and Magoun, 1949) to induce forebrain activation and cortical arousal/waking behavior; however, it is very little known about how brain stem inhibitory inputs affect cholinergic functions. In the current study, glycine, a major inhibitory neurotransmitter of brain stem neurons, and gliotransmitter of local glial cells, was tested for potential interaction with basal forebrain cholinergic (BFC) neurons in male mice. In the BF, glycine receptor α subunit-immunoreactive (GlyRα-IR) sites were localized in choline acetyltransferase (ChAT)-IR neurons. Glycine’s effect on BFC neurons was demonstrated by bicuculline-resistant, strychnine-sensitive spontaneous inhibitory postsynaptic currents (IPSCs; 0.81 ± 0.25 *10-1Hz) recorded in whole cell conditions. Potential neuronal, as well as glial sources of glycine were indicated in the extracellular space of cholinergic neurons by glycine transporter 1 and 2 (GLYT1 and 2)-IR processes found in apposition to ChAT-IR cells. Ultrastructural analyses identified synapses of GLYT2-positive axon terminals on ChAT-IR neurons, as well as GLYT1-positive astroglial processes, which were localized in the vicinity of synapses of ChAT-IR neurons. The brain stem raphe magnus was determined to be a major source of glycinergic axons traced retrogradely from the BF. Our results indicate a direct effect of glycine on BFC neurons. Furthermore, the presence of high levels of plasma membrane glycine transporters in the vicinity of cholinergic neurons suggests a tight control of extracellular glycine in the BF.
All Science Journal Classification (ASJC) codes
- Basal forebrain
- Glycine transporter