Cholinergic modulation of hippocampal cells and circuits - PubMed (original) (raw)

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Cholinergic modulation of hippocampal cells and circuits

Stuart R Cobb et al. J Physiol. 2005.

Abstract

Septo-hippocampal cholinergic fibres ramify extensively throughout the hippocampal formation to release acetylcholine upon a diverse range of muscarinic and nicotinic acetylcholine receptors that are differentially expressed by distinct populations of neurones. The resultant modulation of cellular excitability and synaptic transmission within hippocampal circuits underlies the ability of acetylcholine to influence the dynamic properties of the hippocampal network and results in the emergence of a range of stable oscillatory network states. Recent findings suggest a multitude of actions contribute to the oscillogenic properties of acetylcholine which are principally induced by activation of muscarinic receptors but also regulated through activation of nicotinic receptor subtypes.

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Figures

Figure 1

Figure 1. Activation of septo-hippocampal afferents excites hippocampal pyramidal cells and interneurones

Aa, diagram of septo-hippocampal slice showing relative position of stimulating (within medial septum, MS) and recording electrode (CA3 pyramidal cell). Ab, intracellular recording from a CA3 pyramidal cell reveals an isolated slow depolarizing response to electrical stimulation (indicated by ▴) within the septal nucleus in the presence of a cocktail of AMPA/kainate, NMDA, GABAA and GABAB receptor antagonists (4 μ

m

NBQX, 50 μ

m

CGP40116, 50 μ

m

picrotoxin and 1 μ

m

CGP55845A, respectively). Ac, the action potential discharge and underlying slow depolarizing waveform were abolished upon application of the mAChR antagonist atropine (10 μ

m

). B, example of a similar experiment in which only the AMPA/kainate and NMDA receptor antagonists were present to block glutamatergic EPSPs. The presence of a barrage of IPSPs (shown also in expanded inset) following afferent stimulation suggests a direct cholinergic excitation of presynaptic GABAergic interneurones. Subsequent application of 10 μ

m

atropine abolished IPSP trains in this cell following afferent stimulation (data not shown). Ca, recording from a putative fast-spiking interneurone within area CA1 in which a similar slow depolarizing response is evoked following stimulation of cholinergic afferents. Cb, as with the pyramidal cell response, the slow depolarizing potential is completely abolished upon subsequent coapplication of the mAChR antagonist atropine (10 μ

m

). Detail of evoked cholinergic EPSP methodology given in Morton & Davies (1997).

Figure 2

Figure 2. Pharmacological activation of acetylcholine receptors induces a variety of stable cellular and network oscillatory state

Aa, intracellular recording from a CA3 pyramidal cell reveals a low frequency synchronous burst discharge in response to 1 μ

m

carbachol application. Individual bursts (b) occur within a dominant frequency of 0.15 Hz, as shown in the power spectrum (c). Ba, higher concentration of carbachol (10 μ

m

) results in the appearance of periodic episodes of rhythmic oscillatory depolarization. During oscillatory episodes, rhythmic depolarization was commonly suprathreshold resulting in a phasic dischage of action potentials (b) around the theta frequency range (c). Ca, in some slices, the predominant response to carbachol application is a persistent membrane potential oscillation within the high beta low–gamma frequency range, with the dominant frequency in this example (b) being 29 Hz. D, pharmacological uncoupling of fast AMPA receptor-mediated synaptic transmission (4 μ

m

NBQX) reveals a very slow, presumably intrinsic oscillatory state in a subpopulation of pyramidal neurones, often resembling repeated plateau potentials. Oscillatory states described in A–C developed gradually as carbachol washed into the recording chamber. Each represents a sustained coherent activity within the hippocampal CA3 network that could be readily detected by extracellular field recordings. Oscillatory activity could also be induced rapidly as shown in E where arrowhead indicates fast application of 10 μ

m

carbachol. Methodological details are given in Cobb et al. (1999) and Cobb et al. (2000).

Figure 3

Figure 3. Pharmacological activation of nicotinic acetylcholine receptors modulates synchronized bursting activity in area CA3

A, scatter plot showing instantaneous burst frequency in response to continuous 20 μ

m

bicuculline-induced disinhibition. Following a period of stable burst frequency, application of the selective nAChR agonist DMPP (10 μ

m

) as indicated by the horizontal bar results in a pronounced burst frequency potentiation which is reversed upon subsequent coapplication of the selective nAChR antagonist dihydro-β-erythroidine (30 μ

m

). B, bar chart showing that pharmacological activation of nAChRs produces a significant enhancement of CA3 pyramidal bursting brought about by a range of pharmacological regimes including direct excitation of CA3 neurones through potassium channel blockade-induced depolarization (4-aminopyridine, 10–30 μ

m

4-AP), reduction of fast GABAergic inhibition (20 μ

m

bicuculline) and potentiation of NMDA receptor-mediated excitation (0 m

m

Mg2+ perfusion medium). Methodological details given in Roshan-Milani et al. (2003) from which B is reproduced from Epilepsy Research, 56, Roshan-Milani et al., Regulation of epileptiform activity in hippocampus by micotinic acetylcholine receptor activation. 51–65 © 2003 with permission from Elsevier.

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References

    1. Auerbach JM, Segal M. A novel cholinergic induction of long-term potentiation in rat hippocampus. J Neurophysiol. 1994;72:2034–2040. - PubMed
    1. Behrends JC, ten Bruggencate G. Cholinergic modulation of synaptic inhibition in the guinea pig hippocampus in vitro: excitation of GABAergic interneurons and inhibition of GABA-release. J Neurophysiol. 1993;69:626–629. - PubMed
    1. Brazhnik ES, Fox SE. Action potentials and relations to the theta rhythm of medial septal neurons in vivo. Exp Brain Res. 1999;127:244–258. - PubMed
    1. Burgard EC, Sarvey JM. Muscarinic receptor activation facilitates the induction of long-term potentiation (LTP) in the rat dentate gyrus. Neurosci Lett. 1990;116:34–39. - PubMed
    1. Buzsaki G. Theta oscillations in the hippocampus. Neuron. 2002;33:325–340. - PubMed

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