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Optogenetic Entrainment of Hippocampal Theta Oscillations in Behaving Mice
Published on: June 29, 2018
Coincident activation of mGluRs and mAChRs imposes theta frequency patterning on synchronised network activity in the
S R Cobb1, D O Bulters, C H Davies
1Department of Neuroscience, 1 George Square, University of Edinburgh, Edinburgh EH8 9JZ, UK. s.cobb@bio.gla.ac.uk
Abstract:
Activation of metabotropic glutamate receptors (mGluRs) with the broad spectrum mGluR agonist 1S,3R ACPD (10-50 microM) induced spontaneous field potentials at low frequencies ('burst-mode' activity; <1 Hz) in the CA3 region of rat hippocampal slices. At higher concentrations (100-400 microM) ACPD switched this form of activity to a second, more complex pattern of activity in which intermittent episodes of theta frequency oscillations predominated ('theta-mode' activity; 4-14 Hz). Both patterns of activity were evoked by selective activation of group I mGluRs and, in particular, could be induced by activation of mGluR5 alone using the subtype selective agonist CHPG (0.5-5 mM). In contrast, activation of group II mGluRs (DCG IV; 100 microM) produced only burst-mode behaviour whilst activation of group III mGluRs (L-AP4; 100 microM) did not result in synchronised network activity. Concurrent extra- and intracellular recordings demonstrated that this mGluR-induced theta-mode activity represented the synchronous firing of CA3 pyramidal cells and that it shared a similar temporal signature to that generated by activation of muscarinic acetylcholine receptors (mAChRs). Furthermore, application of mGluR and mAChR agonists at concentrations sufficient to produce only burst-mode activity when applied individually, produced theta-mode activity when co-applied. These data suggest that the level of activation of different mGluRs and mAChRs crucially determine the pattern of rhythmical network activity generated in the hippocampal CA3 network. These results also indicate that individual receptor subtypes (i.e. mGluR5) can initiate patterns of coherent network activity but that interactions between the cholinergic and glutamatergic transmitter systems may also be important factors in governing the temporal patterning of hippocampal network activity.
Insights
Activation of metabotropic glutamate receptors (mGluRs) in the hippocampus influences network activity patterns. Specific mGluR subtypes, like mGluR5, can initiate theta-mode activity, suggesting complex interactions in neural signaling.
Area of Science:
- Neuroscience
- Neurophysiology
- Receptor Pharmacology
Background:
- Metabotropic glutamate receptors (mGluRs) are crucial modulators of synaptic transmission and neuronal excitability in the central nervous system.
- The CA3 region of the hippocampus is a key area for memory formation and exhibits complex network dynamics.
- Understanding how specific receptor activations influence network oscillations is vital for deciphering neural circuit function.
Purpose of the Study:
- To investigate the effects of activating different metabotropic glutamate receptor (mGluR) groups and subtypes on network activity in the rat hippocampal CA3 region.
- To characterize the patterns of spontaneous field potentials induced by mGluR activation, specifically 'burst-mode' and 'theta-mode' activity.
- To explore the role of mGluR5 and its interaction with muscarinic acetylcholine receptors (mAChRs) in generating synchronized network activity.
Main Methods:
- Extracellular and intracellular recordings were performed on rat hippocampal slices.
- Pharmacological activation of mGluRs using agonists like 1S,3R ACPD, CHPG (mGluR5 selective), DCG IV (group II selective), and L-AP4 (group III selective).
- Co-application of mGluR and mAChR agonists to assess synergistic effects on network activity.
Main Results:
- Broad spectrum mGluR activation (1S,3R ACPD) induced low-frequency 'burst-mode' activity (<1 Hz) at lower concentrations and higher-frequency 'theta-mode' activity (4-14 Hz) at higher concentrations.
- Group I mGluRs, particularly mGluR5 activation (CHPG), were sufficient to induce both burst-mode and theta-mode activity.
- Group II mGluRs induced only burst-mode activity, while group III mGluRs did not induce synchronized network activity. Theta-mode activity involved synchronous firing of CA3 pyramidal cells and shared characteristics with mAChR-induced activity. Co-application of mGluR and mAChR agonists produced theta-mode activity.
Conclusions:
- The pattern of hippocampal CA3 network activity (burst-mode vs. theta-mode) is critically dependent on the degree of activation of different mGluRs and mAChRs.
- Individual receptor subtypes, such as mGluR5, can initiate coherent network activity patterns.
- Interactions between glutamatergic and cholinergic systems play a significant role in regulating the temporal patterning of hippocampal network activity.
