Insulin modulates network activity in olfactory bulb slices: impact on odour processing

Abstract

Key pointsr Olfactory function is largely under metabolic influence. r Insulin, one of the major players between food intake and energy balance, is known to act at both central and peripheral levels.r The present study assesses the action of insulin in olfactory bulb slices by using patch-clamp recordings in young rats.r The results show that insulin can alter both spontaneous and olfactory nerve-induced firing activities in most of the main ouput neurons, this action being differentially exerted in two opposite directions. r A mathematical model demonstrates that insulin, by acting in this way, could impact odour detection and discrimination mechanisms. Such an impact could be hypothesized as being exerted according to pertinent ecological characteristics, such as the alimentary/ethological valence of odour.Abstract Odour perception depends closely on nutritional status, in animals as in humans. Insulin, the principal anorectic hormone, appears to be one of the major candidates for ensuring the link between olfactory abilities and nutritional status, by modifying processing in the olfactory bulb (OB), one of its main central targets. The present study investigates whether and how insulin can act in OB, by evaluating its action on the main output neurons activities, mitral cells (MCs), in acute rat OB slices. Insulin was found to act at two OB network levels: (1) on MCs, by increasing their excitability, probably by inhibiting two voltage-gated potassium (K + ) channels; (2) on interneurons by modifying the GABAergic and on glutamatergic synaptic activity impinging on MCs, mainly reducing them. Insulin also altered the olfactory nerve (ON)-evoked excitatory postsynaptic currents in 60% of MCs. Insulin decreased or increased the ON-evoked responses in equal proportion and the direction of its effect depended on the initial neuron ON-evoked firing rate. Indeed, insulin tended to decrease the high and to increase the low ON-evoked firing rates, thereby reducing inter-MC response firing variability. Therefore, the effects of insulin on the evoked firing rates were not carried out indiscriminately in the MC population. By constructing a mathematical model, the impact of insulin complex effects on OB was assessed at the population activity level. The model shows that the reduction of variability across cells could affect MC detection and discrimination abilities, mainly by decreasing and, less frequently, increasing them, depending on odour quality. Thus, as previously proposed, this differential action of insulin on N. Kuczewski and N. Fourcaud-Trocmé contributed equally to this work.

Insulin Modulates Neural Activity of Pyramidal Neurons in the Anterior Piriform Cortex

“…In addition to the excitatory effect, we also found an inhibitory effect of insulin on a minority of pyramidal neurons in slice recording. This complicated dual modulation was also observed in mitral cells of the OB ( Kuczewski et al, 2014 ). A mathematical model has been established and predicts that the complicated action of insulin could impact odor detection and discrimination in opposite directions depending on the odor quality ( Kuczewski et al, 2014 ).…”

“…For example, the molecular mechanisms of how insulin affects mitral cells have been revealed by identifying Kv1.3 as a substrate for insulin-mediated phosphorylation in the OB ( Fadool et al, 2000 , 2011 ; Colley et al, 2004 ). Moreover, a recent study deciphered how insulin modulates the neural activity of mitral cells in slice recording and a mathematical model was established to explain how insulin impacts odor detection and discrimination ( Kuczewski et al, 2014 ).…”

Expression of feeding-related neuromodulatory signalling molecules in the mouse central olfactory system

“…Intracerebroventricular (icv) administration of the orexigenic neuropeptide orexin into rats promoted sniffing behaviour and c-fos expression in response to food odour in the OB, while icv administration of the anorexigenic compound leptin decreased these responses 27 . Application of orexin to the sliced OB potentiated odour-induced firing activity of the projecting neurons of the OB (mitral cells) 28 , while anorexigenic insulin modulated the activity of mitral cells and interneurons in the OB 29,30 . Endocannabinoid signals to the OB potentiate feeding behaviour under fasting conditions 31 .…”

Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice

“…Our current data demonstrate no change in odorant discrimination or threshold when insulin is administered in a daily regimen. It is well known that insulin modulates mitral cell (MC) firing frequency when applied acutely [20, 51, 52] as a driver of state-dependent odor processing that could affect olfactory ability during fasting or satiety states [16, 20, 53, 54]. During the postprandial period of insulin release, untreated animals would be expected to respond to such insulin fluctuations, whereas our chronic insulin IND-treated animals with already elevated plasma insulin levels would be predicted to not electrically detect a new insulin baseline by exhibiting altered MC activity.…”