Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis.

Two autoimmune murine models--proteoglycan (aggrecan)-induced arthritis (PGIA) and collagen-induced arthritis (CIA)--were developed in parent strains, F1 and F2 hybrids of major histocompatibility complex (MHC)-matched (H-2) BALB/c x DBA/2 and MHC-unmatched (H-2/H-2) BALB/c x DBA/1 intercrosses. The major goal of this comparative study was to identify disease (model)-specific (PGIA or CIA) and shared clinical and immunologic loci in 2 types of genetic intercrosses. Qualitative (binary/susceptibility) and quantitative (severity and onset) clinical trait loci were separated and analyzed independently or together with various pathophysiologic/immunologic traits, such as antigen-specific T- and B-cell responses and cytokine production. The major quantitative trait locus (QTL) was the MHC on chromosome 17, which was especially dominant in CIA. In addition, chromosomes 3, 5, 10, and X contained shared clinical loci in both models, and a total of 8 QTLs (clinical traits together with immunologic traits) were colocalized in PGIA and CIA.

Interaural intensity difference processing in auditory midbrain neurons: effects of a transient early inhibitory input.

Interaural intensity differences (IIDs) are important cues that animals use to localize high-frequency sounds. Neurons sensitive to IIDs are excited by stimulation of one ear and inhibited by stimulation of the other ear, such that the response magnitude of the cell depends on the relative strengths of the two inputs, which in turn depends on the sound intensities at the ears. In the auditory midbrain nucleus, the inferior colliculus (IC), many IID-sensitive neurons have response functions that decline steeply from maximum to zero spikes as a function of IID. However, there are also many neurons with much more shallow response functions that do not decline to zero spikes. We present evidence from single-unit recordings in the Free-tailed bat's IC that this partially inhibited response pattern is a result of the inhibitory input to these cells being very brief ( approximately 2 msec). Of the cells sampled, 54 of 137 (40%) achieved partial inhibition when tested with 60 msec tones, and the inhibition to these 54 cells occurred primarily during the first few milliseconds of the excitatory response. Consequently, the initial component of the response was highly sensitive to IIDs, whereas the later component was primarily insensitive to IIDs. Each of the 54 "partially inhibited" cells was able to reach complete inhibition with very short stimuli, such as simulated bat echolocation calls that invoked only the initial, IID-sensitive component. Local application of inhibitory transmitter antagonists disabled the short inhibitory input, indicating that this response pattern is created within the IC.