Noradrenergic regulation of hippocampal place cells

The influence of noradrenergic input to the hippocampus was assessed by recording hippocampal place cells and by modulating the noradrenergic tone with a selective agonist and antagonist of the alpha2-autoreceptors. The rats received intraperitoneal injection of 5 microg/kg of dexmedetomidine (DEX), an alpha2-agonist, 0.2 mg/kg of atipamezole (ATI), an alpha2-antagonist, or saline. Hippocampal place cells were recorded in a familiar rectangular environment and in three types of new environments (rectangle, square, and cylinder). Recordings in the familiar environment were conducted in two phases, either before (early phase) or after (late phase) the exposure to new environments. In the familiar environment, DEX significantly increased the mean firing rate of hippocampal interneurons, while ATI increased the mean firing rate of pyramidal cells. Only ATI in the early phase of the experiment impaired spatial selectivity. Both drugs induced field rotations in the early phase of the study, but in the late phase DEX decreased, while ATI increased field stability in the familiar environment. The drug effects in the new environment were dependent on degree of novelty. No difference between treatments was observed in the new rectangle, but in the square and cylinder, ATI increased the mean firing rate, number of fields, and field area compared to other treatments. Stability of the original firing fields in the familiar rectangle was dependent on type of interfering environment and drug treatment. Exposure to another rectangle had the smallest impact, and exposure to a square the largest impact, on the original field pattern. ATI impaired stability of the original field after exposure to a rectangular and cylinder, while the impairing effect of DEX was only observed after exposure to a cylinder. In conclusion, increased noradrenergic tone increases the firing rate of hippocampal place cells, especially when the experimental situation and environment are new, but this increase is spatially nonselective. Furthermore, manipulation of the noradrenergic tone in either direction leads to instability of firing fields.