Glutamate in thalamic fibers terminating in layer IV of primary sensory cortex

Biochemical and pharmacological experiments support glutamate (Glu) as a thalamocortical transmitter, but do not distinguish direct from indirect effects (via excitation of glutamergic corticocortical fibers); anatomical studies to date have yielded variable results. We identified thalamocortical terminals in layer IV of primary somatic sensory, auditory, and visual cortex by injecting WGA-HRP in the corresponding thalamic sensory relay nuclei of rats. Terminals from each thalamic nucleus were similar, containing abundant mitochondria and loosely packed clear vesicles; they made asymmetric synaptic contacts mainly with dendritic spines. After tracer injections into nearby regions of cortex, most terminals also made asymmetric contacts mainly onto spines, but these corticocortical terminals were smaller, containing sparse mitochondria and densely packed clear vesicles. GABAergic terminals (identified by postembedding immunogold staining) made symmetric synapses mainly onto dendritic shafts; those terminating near thalamocortical terminals were also large and contained abundant mitochondria. To determine whether Glu is enriched in thalamocortical terminals, we performed postembedding double-labeling immunocytochemistry for Glu and GABA, using different gold particle sizes. The density of particles coding for Glu was significantly enriched over identified thalamocortical terminals, in comparison to nearby dendrites, astrocytes, and GABAergic terminals, and this enrichment was similar for all three sensory areas. The degree of enrichment in thalamocortical terminals, but not in GABAergic terminals, was linearly related to vesicle density. We conclude that Glu is likely to be a neurotransmitter for thalamocortical relay neurons.