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Hippocampal field CA1 interneuronal nociceptive responses: modulation by medial septal region and morphine
Insights
Formalin injection excites dorsal hippocampus GABAergic interneurons, modulated by theta activity. Morphine
Area of Science:
- Neuroscience
- Pain Research
- Hippocampal Circuitry
Background:
- GABAergic interneurons in the hippocampus play a critical role in regulating neuronal activity.
- The dorsal hippocampus (field CA1) is involved in processing sensory information, including pain.
- The medial septal region influences hippocampal theta rhythm and neuronal activity.
Purpose of the Study:
- To investigate the effect of noxious stimuli on hippocampal CA1 GABAergic interneurons.
- To explore the role of the medial septal region in mediating these responses.
- To examine the influence of morphine on these interneurons and its interaction with the septohippocampal network.
Main Methods:
- Extracellular recordings of putative GABAergic interneurons in the dorsal hippocampus (field CA1) of urethane-anesthetized rats.
- Formalin injection to induce a noxious stimulus.
- Administration of morphine and naloxone.
- Medial septal region lesions.
Main Results:
- Formalin injection excited a majority of CA1 GABAergic interneurons, often synchronized with theta activity.
- Concurrent morphine administration initially increased, then decreased, interneuron activity and theta.
- Morphine's effects were naloxone-reversible, while morphine alone decreased firing rate.
- Medial septal lesions abolished formalin-induced excitation and prevented morphine-induced decreases in interneuron activity.
Conclusions:
- CA1 GABAergic interneurons are involved in suppressing pyramidal cell activity during noxious stimuli, mediated by the medial septal region.
- Morphine modulates hippocampal pain responses via the septohippocampal neural network.
- These findings shed light on the neural mechanisms of pain processing and opioid action in the hippocampus.
Abstract:
A majority (24/32) of the extracellularly recorded dorsal hippocampus field CA1 putative GABAergic interneurons were excited in conjunction with theta activation on formalin injection (5%, 0.05 ml, s.c. into right hind-paw) in urethane (1.0 g/kg, i.p.)-anaesthetized rats. An increase in activity was observed to the 10th minute (n=24) and also at later time-periods at which a few of the neurons were recorded following injection of formalin. The mean peak increase in activity within 5 min of formalin injection was 6.43+/-0.81 Hz over the average background activity for these neurons (6.46+/-1.04 Hz). Of 24 neurons, 14 exhibited an increase in activity which was rhythmically modulated with theta. With a concurrent administration of formalin and morphine (5 mg/kg, i.p.), the presumed interneurons recorded displayed an initial increase in discharge rate (mean peak increase within 5 min of 6.95+/-1.10 Hz) which then declined with a decrease in theta activity. The effect of concurrent morphine was naloxone reversible. Morphine administration alone resulted in an immediate decrease in the interneuronal firing rate. In presence of the medial septal region lesions, formalin did not evoke an excitation of intemeurons or theta activation. Further, such lesions prevented the decrease in intemeuron activity to morphine administration. The above data are consistent with the notion that (i) the field CA1 interneurons participate in a noxious stimulus-induced and medial septal region mediated pyramidal cell suppression, and (ii) morphine affects CA1 nociceptive responses partly in a fashion consistent with the effect of the drug on septohippocampal neural network processing.
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