Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.
Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaf...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-07-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC5521875?pdf=render |
| _version_ | 1818478652146319360 |
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| author | Roman A Sandler Dustin Fetterhoff Robert E Hampson Sam A Deadwyler Vasilis Z Marmarelis |
| author_facet | Roman A Sandler Dustin Fetterhoff Robert E Hampson Sam A Deadwyler Vasilis Z Marmarelis |
| author_sort | Roman A Sandler |
| collection | DOAJ |
| description | Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs. |
| first_indexed | 2024-12-10T09:50:23Z |
| format | Article |
| id | doaj.art-703e5e872db7428580ff6fce5b939263 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-10T09:50:23Z |
| publishDate | 2017-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-703e5e872db7428580ff6fce5b9392632022-12-22T01:53:41ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582017-07-01137e100562410.1371/journal.pcbi.1005624Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.Roman A SandlerDustin FetterhoffRobert E HampsonSam A DeadwylerVasilis Z MarmarelisMuch of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.http://europepmc.org/articles/PMC5521875?pdf=render |
| spellingShingle | Roman A Sandler Dustin Fetterhoff Robert E Hampson Sam A Deadwyler Vasilis Z Marmarelis Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3. PLoS Computational Biology |
| title | Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3. |
| title_full | Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3. |
| title_fullStr | Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3. |
| title_full_unstemmed | Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3. |
| title_short | Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3. |
| title_sort | cannabinoids disrupt memory encoding by functionally isolating hippocampal ca1 from ca3 |
| url | http://europepmc.org/articles/PMC5521875?pdf=render |
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