Investigating Olfactory Sensory Neurons Facilitation For Aerobic Exercise-induced Spatial Memory Improvement

Abstract

Introduction: The positive effects of exercise on spatial memory and learning have been demonstrated in research. The olfactory sensory neurons (OSNs) respond to mechanical stimulation induced by nasal airflow which is associated with airflow intensity. Accordingly, nasal breathing can modulate brain oscillations in nonolfactory areas, and respiration-entrained oscillations aid the improvement of cognitive abilities. Given that aerobic exercise increases the rate of respiration and intensity of nasal airflow, this study evaluates the role of OSNs in mediating the effects of aerobic exercise on memory.

Methods: We examined spatial memory following exercise in animal models of olfactory sensory neuron impairment (methimazole injection 300 mg/kg/week).

Results: Destroying OSNs significantly reduces olfactory bulb (OB) activity at delta and theta frequency bands as well as its coupling to respiration. More importantly, it abolished the positive effect of exercise on spatial memory (P<0.05).

Conclusion: The OB activity is one of the probable mechanisms for improving spatial memory following exercise.

Keywords: Aerobic exercise; Local field potentials(LFPs); Olfactory bulb (OB); Spatial memory.

Figure 1.

Experimental design A) The timeline of the study design (the rats received intraperitoneal injections of saline or methimazole (300 mg/kg) every week and LFP was recorded at the end of any seven weeks after the last session (five days/week) of exercise). B) A schematic representation of the electrode implantation site on the rat head, C) The histological confirmation of a recording site in OB Abbreviations: R: Recovery; E: Exercise; LFP: Local field potential; ISM: Injection saline or methimazole; BT: Behavioral tests; OB: Olfactory bulb.

Figure 2.

Aerobic exercise increasing the number of neurons A) Cresyl violet staining of the OB in four groups (scale bar=20 μm) (numerous granule cells (↑) can be observed), B) Neuronal count of cresyl violet stained tissues. Notes: Values are expressed as Mean±SEM. The data were analyzed by the two-way ANOVA, followed by Tukey post hoc test; ^*Significant compared to the C-S group, ^#Significant compared to the E-S group, ^$Significant compared to the C-M group. Abbreviations: C-S: Control saline; C-M: Control methimazole; E-S: Exercise saline; E-M: Exercise methimazole.

Figure 3.

a) The power comparison of delta (<4 Hz) theta (4–12 Hz) and OB frequencies in seven weeks (the power of OB decreased during a seven-week period), b) The statistical comparison of delta and theta frequencies (the power of OB in delta and theta frequencies significantly decreased in the 7^th week compared to the first week, c, d) A comparison of delta (<4 Hz) and theta (4–12 Hz) in 4 groups (the exercise increased power in the 7^th week compared to the 1^st week, and methimazole prevented this increase Notes: Values are expressed as the Mean±SEM. The data were analyzed by t-test in the methimazole group and three-way repeated-measures ANOVA in weeks one and seven; ^**P<0.01, ^*Significant difference with saline, ^#Significant difference with week one, ^$Significant difference with the control group. Abbreviations: PSD: Power spectral density; OB: Olfactory bulb; C-S: Control saline; C-M: Control methimazole; E-S: Exercise saline; E-M: Exercise methimazole.

Figure 4.

a, b, c, d) The maximum respiration-OB cross-correlation values in four groups (exercise improved the correlation between respiration and OB oscillations), e) Comparison of cross-correlation values between the four groups in week 7, f, g, h, i) The representative traces of LFP from OB and breathing in four groups Notes: Values are expressed as Mean±SEM. The data were analyzed by t-test; ^*P<0.05. Abbreviations: OB: Olfactory bulb; LFP: Local field potential; C-S: Control saline; C-M: Control methimazole; E-S: Exercise saline; E-M: Exercise methimazole; In: Inhalation; Ex: Exhalation.

Figure 5.

a, b) The escape latency and the latency to first recorded in the training trial, c) The schematic representation of the Barnes maze and Barnes maze heat maps in the four-group probe trial (the color scale represents the time of visits to the maze (min and max), d) The ratio of GS to NGS explorations, e) The total distance and percentage of mobility in for groups Notes: All animals had normal locomotor activity. Values are expressed as Mean±SEM. The data were analyzed by two-way ANOVA. ^*Significant compared to the CS group,^#Significant compared to the ES group, ^$Significant compared to the CM group. Abbreviations: d: Cohen d; C-S: Control saline; C-M: Control methimazole; E-S: Exercise saline; E-M: Exercise methimazole; G-S: Goal sector; NGS: Non-goal sector.