Abstract
Aim:
Spiking activities and neuronal network oscillations in the theta frequency range have been found in many cortical areas during information processing. The aim of this study is to determine whether nicotinic acetylcholine receptors (nAChRs) mediate neuronal network activity in rat medial septum diagonal band Broca (MSDB) slices.
Methods:
Extracellular field potentials were recorded in the slices using an Axoprobe 1A amplifier. Data analysis was performed off-line. Spike sorting and local field potential (LFP) analyses were performed using Spike2 software. The role of spiking activity in the generation of LFP oscillations in the slices was determined by analyzing the phase-time relationship between the spikes and LFP oscillations. Circular statistic analysis based on the Rayleigh test was used to determine the significance of phase relationships between the spikes and LFP oscillations. The timing relationship was examined by quantifying the spike-field coherence (SFC).
Results:
Application of nicotine (250 nmol/L) induced prominent LFP oscillations in the theta frequency band and both small- and large-amplitude population spiking activity in the slices. These spikes were phase-locked to theta oscillations at specific phases. The Rayleigh test showed a statistically significant relationship in phase-locking between the spikes and theta oscillations. Larger changes in the SFC were observed for large-amplitude spikes, indicating an accurate timing relationship between this type of spike and LFP oscillations. The nicotine-induced spiking activity (large-amplitude population spikes) was suppressed by the nAChR antagonist dihydro-β-erythroidine (0.3 μmol/L).
Conclusion:
The results demonstrate that large-amplitude spikes are phase-locked to theta oscillations and have a high spike-timing accuracy, which are likely a main contributor to the theta oscillations generated in MSDB during nicotine receptor activation.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Berry SD, Thompson RF . Prediction of learning rate from the hippocampal electroencephalogram. Science 1978; 200: 1298–300.
Hwang EJ, Andersen RA . Effects of visual stimulation on LFPs, spikes, and LFP-spike relations in PRR. J Neurophysiol 2011; 105: 1850–60.
Rutishauser U, Ross IB, Mamelak AN, Schuman EM . Human memory strength is predicted by theta-frequency phase-locking of single neurons. Nature 2010; 464: 903–7.
Buzsaki G . Theta oscillations in the hippocampus. Neuron 2002; 33: 325–40.
Cantero JL, Atienza M, Stickgold R, Kahana MJ, Madsen JR, Kocsis B . Sleep-dependent theta oscillations in the human hippocampus and neocortex. J Neurosci 2003; 23: 10897–903.
Kahana MJ, Sekuler R, Caplan JB, Kirschen M, Madsen JR . Human theta oscillations exhibit task dependence during virtual maze navigation. Nature 1999; 399: 781–4.
Lee H, Simpson GV, Logothetis NK, Rainer G . Phase locking of single neuron activity to theta oscillations during working memory in monkey extrastriate visual cortex. Neuron 2005; 45: 147–56.
Pare D, Gaudreau H . Projection cells and interneurons of the lateral and basolateral amygdala: distinct firing patterns and differential relation to theta and delta rhythms in conscious cats. J Neurosci 1996; 16: 3334–50.
Jacobs J, Kahana MJ, Ekstrom AD, Fried I . Brain oscillations control timing of single-neuron activity in humans. J Neurosci 2007; 27: 3839–44.
Kwag J, Paulsen O . Bidirectional control of spike timing by GABA(A) receptor-mediated inhibition during theta oscillation in CA1 pyramidal neurons. Neuroreport 2009; 20: 1209–13.
Anderson S . Theta phase-locked spike timing in the hippocampus: predicting strong memories. Neurosurgery 2010; 67: N17–19.
Leranth C, Vertes RP . Median raphe serotonergic innervation of medial septum/diagonal band of broca (MSDB) parvalbumin-containing neurons: possible involvement of the MSDB in the desynchronization of the hippocampal EEG. J Comp Neurol 1999; 410: 586–98.
Borhegyi Z, Varga V, Szilagyi N, Fabo D, Freund TF . Phase segregation of medial septal GABAergic neurons during hippocampal theta activity. J Neurosci 2004; 24: 8470–9.
Lu CB, Ouyang G, Henderson Z, Li X . Induction of theta-frequency oscillations in the rat medial septal diagonal band slice by metabotropic glutamate receptor agonists. Neuroscience 2011; 177: 1–11.
Klemm WR . Effects of electric stimulation of brain stem reticular formation on hippocampal theta rhythm and muscle activity in unanesthetized, cervical- and midbrain-transected rats. Brain Res 1972; 41: 331–44.
Oh JD, Butcher LL, Woolf NJ . Thyroid hormone modulates the development of cholinergic terminal fields in the rat forebrain: relation to nerve growth factor receptor. Brain Res Dev Brain Res 1991; 59: 133–42.
Wu J, George AA, Schroeder KM, Xu L, Marxer-Miller S, Lucero L, et al. Electrophysiological, pharmacological, and molecular evidence for alpha7-nicotinic acetylcholine receptors in rat midbrain dopamine neurons. J Pharmacol Exp Ther 2004; 311: 80–91.
Song C, Murray TA, Kimura R, Wakui M, Ellsworth K, Javedan SP, et al. Role of alpha7-nicotinic acetylcholine receptors in tetanic stimulation-induced gamma oscillations in rat hippocampal slices. Neuropharmacology 2005; 48: 869–80.
Lu CB, Henderson Z . Nicotine induction of theta frequency oscillations in rodent hippocampus in vitro. Neuroscience 2010; 166: 84–93.
Shrager Y, Kirwan CB, Squire LR . Activity in both hippocampus and perirhinal cortex predicts the memory strength of subsequently remembered information. Neuron 2008; 59: 547–53.
Lu CB, Yanagawa Y, Henderson Z . Properties of gamma frequency oscillatory activity induced in hippocampal slices from the adult GAD67-GFP (Deltaneo) mouse. Brain Res 2010; 1323: 65–73.
Garner HL, Whittington MA, Henderson Z . Induction by kainate of theta frequency rhythmic activity in the rat medial septum-diagonal band complex in vitro. J Physiol 2005; 564: 83–102.
Carretie L, Hinojosa JA, Albert J, Mercado F . Neural response to sustained affective visual stimulation using an indirect task. Exp Brain Res 2006; 174: 630–7.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (grant No 31070938 and No 81271422), the open project of the State Key Laboratory of Cognitive Neuroscience and Learning in Beijing Normal University (time periods: form 2012 to 2013), Hebei applied basic research plan key program for basic research of China (grant No 12966119D), Natural Science Foundation of Hebei Province of China (grant No H2012203067), Specialized Research Fund for the Doctoral Program of Higher Education of China (grant No 20101333110006), Hebei Province Department of Education Fund (grant No 2010285) and UK Medical Research Council (grant No G0500823).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wen, D., Peng, C., Ou-yang, Gx. et al. Effects of nicotine stimulation on spikes, theta frequency oscillations, and spike-theta oscillation relationship in rat medial septum diagonal band Broca slices. Acta Pharmacol Sin 34, 464–472 (2013). https://doi.org/10.1038/aps.2012.180
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2012.180
