Dihydrokainate restores recall of olfactory reward‐based associative learning following impairment by isoflurane

The mammalian olfactory bulb (OB) shapes olfactory discriminative perception, however, its role in olfactory associative learning is less clear. We trained adult CD‐1 mice (12 trials) to associate a test odor (conditioned stimulus) with a 5 mg, 100% sucrose pellet reward (unconditioned stimulus). Recall of odor discriminative learning was tested (30 mins later) with a series (n=4) of chemically related compounds of increasing dissimilarity. We now report that brief (15 min) exposure to 1% or 2% isoflurane (iso) significantly impaired recall of olfactory discriminative associative learning (P = 0.0001 vs no iso) without causing hypoxia. High (2%) iso also impaired recall of visual associative learning (P< .005 vs no iso). Recall of olfactory learning was unchanged despite allowing 15 min for consolidation (before iso) or 60 min recovery (after iso). Bulbar infusion of 1 mM or 10 mM dihydrokainate (DHK), a specific antagonist of the high affinity glutamate transporter (GLT1), completely restored recall of olfactory associative learning following isoflurane (P< .005 vs vehicle). Bilateral OB infusion of 10 mM DHK had no effect on impairment of visual associative learning by isoflurane (P < .001 vs no iso). These data are consistent with a mechanism for isoflurane‐induced olfactory retrograde amnesia involving an increased rate of glutamate uptake (via GLT1) in the olfactory bulb. Grant Funding Source : NIDCD, Cornell Hughes Scholars Program