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Neurons of the subthalamic nucleus play a key role in the normal physiology and the pathophysiology of the basal ganglia. In order to understand better how the activity of subthalamic neurons and hence the output of the basal ganglia are controlled, we have reexamined the topography and examined in detail the synaptology and neurochemical nature of the two major excitatory projections to the subthalamic nucleus, that from the cortex and from the parafascicular nucleus of the thalamus. The approach was to use anterograde neuronal tracing and postembedding immunocytochemistry for amino acid transmitters. In confirmation of previous findings the cortical and thalamic projections were topographically organized, although the topography was more finely organized, and the projections more extensive, than previously demonstrated. Cortical and thalamic terminals made asymmetrical synaptic contacts with the dendrites and spines of subthalamic neurons. The thalamic terminals contacted larger postsynaptic targets, and therefore presumably more proximal regions of subthalamic neurons, than did the cortical terminals. Quantitative analysis of the postembedding immunolabelled sections revealed that the cortical and thalamic terminals were significantly enriched in glutamate-immunoreactivity when compared to identified gamma-aminobutyric acid (GABA)-positive terminals, supporting physiological studies that suggest that these projections use glutamate as their neurotransmitter. In addition a small population of nonanterogradely labelled terminals that formed asymmetrical synapses and were immunopositive for GABA were identified. A larger population of terminals that formed symmetrical synapses were also immunopositive for GABA and were probably derived from the globus pallidus. The latter type of terminal was found to make convergent synaptic input with cortical or thalamic terminals on the dendrites and spines of subthalamic neurons, indicating that the "indirect pathways" by which information flows through the basal ganglia converge at the level of individual neurons in the subthalamic nucleus.

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Pneumonia causes short‐ and long‐term cognitive dysfunction in a high proportion of patients, although the mechanism(s) responsible for this effect are unknown. Here, we tested the hypothesis that pneumonia‐elicited cytotoxic amyloid and tau variants: (1) are present in the circulation during infection; (2) lead to impairment of long‐term potentiation; and, (3) inhibit long‐term potentiation dependent upon tau. Cytotoxic amyloid and tau species were recovered from the blood and the hippocampus following pneumonia, and they were present in the extracorporeal membrane oxygenation oxygenators of patients with pneumonia, especially in those who died. Introduction of immunopurified blood‐borne amyloid and tau into either the airways or the blood of uninfected animals acutely and chronically impaired hippocampal information processing. In contrast, the infection did not impair long‐term potentiation in tau knockout mice and the amyloid‐ and tau‐dependent disruption in hippocampal signaling was less severe in tau knockout mice. Moreover, the infection did not elicit cytotoxic amyloid and tau variants in tau knockout mice. Therefore, pneumonia initiates a tauopathy that contributes to cognitive dysfunction.

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