Novelty‐elicited, Noradrenaline‐dependent Enhancement of Excitability in the Dentate Gyrus

Abstract

In order to relate noradrenaline-dependent potentiation in the dentate gyrus to behavioural events, rats were made to explore an environment in which their encounters with novel stimuli could be strictly controlled and monitored. Previous experiments have shown that an encounter with novel objects in a holeboard elicits a burst response in a large population of noradrenergic neurons of the locus coeruleus. Such a burst response has been demonstrated to produce a large and transient potentiation of the population spike in the dentate gyrus. In the present series of experiments, rats were chronically implanted with stimulating electrodes in the perforant pathway and recording electrodes in the dentate gyrus. Evoked potentials were monitored in the awake rat, first while it was resting quietly in a familiar environment and then while it was exploring the holeboard containing a novel object in a specific hole. There was a tonic increase in population spike amplitude when the rat was placed in the novel holeboard environment, but this effect gradually dissipated. This increase was partly blocked by the beta-noradrenergic antagonist propranolol. In addition there was a robust phasic increase in spike amplitude when the rat encountered a novel stimulus. This phasic response lasted approximately 50-75 s and was absent in animals treated with propranolol. These results show that a behavioural encounter with a novel stimulus can transiently enhance information transmission through the hippocampus, and suggest that activation of the noradrenergic system by the novel stimulus mediates this behavior-dependent gating.

Locus Ceruleus Activation Suppresses Feedforward Interneurons and Reduces β-γ Electroencephalogram Frequencies While It Enhances θ Frequencies in Rat Dentate Gyrus

“…In awake rats exploring novel objects, an increase in the perforant path-evoked population spike dependent on ␤-adrenoceptors is observed for ϳ1 min (Kitchigina et al, 1997). This increase is likely related to phasic firing of locus ceruleus, which accompanies novel object exploration, silencing feedforward interneurons as in this study.…”

“…Long-term potentiation of the perforant path-evoked field potential in the dentate gyrus after locus ceruleus activation (Harley and Milway, 1986;Harley and Sara, 1992;Kitchigina et al, 1997; or after reinforcer-induced switching from early-phase to late-phase tetanic long-term potentiation (Seidenbecher et al, 1997) is ␤-adrenoceptor dependent, consistent with a requirement for norepinephrine. Potentiation of the perforant path population spike by norepinephrine, the characteristic in vivo effect, could arise from increased granule cell excitability or reduced inhibition from interneurons on granule cells, or both.…”

“…This increase is likely related to phasic firing of locus ceruleus, which accompanies novel object exploration, silencing feedforward interneurons as in this study. Rats moving into novel environments also show dramatic and transient disinhibition of unit activity in hippocampus (Wilson and McNaughton, 1993), and evoked potential parameters, such as population spike amplitude, are elevated (Kitchigina et al, 1997).…”

“…Locus ceruleus activation by novelty is associated with increases in the perforant path-evoked population spike (Kitchigina et al, 1997). Glutamate infusion into locus ceruleus also phasically activates locus ceruleus neurons and is associated with an increased perforant path population spike (Harley and Sara, 1992).…”

Mode shifting between storage and recall based on novelty detection in oscillating hippocampal circuits

“…Over the past decades, the hippocampus has been implicated in various functions, including episodic memory (Squire, 1992;Eichenbaum et al, 1999) and novelty detection of the contextual or spatial aspects of an experience (Johnson and Moberg, 1980;Kitchigina et al, 1997;Zhu et al, 1997;Knight and Nakada, 1998;Xiang and Brown, 1998;Montag-Sallaz et al, 1999;Lisman and Otmakhova, 2001;Mumby et al, 2002). From existing experimental studies, it is difficult to understand how these functions are interrelated, and whether they are subserved by the same processes or by different ones at the circuit level.…”