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Endocannabinoids modulate encoding of sequential memory in the rat hippocampus

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Abstract

Rationale

This report investigated the role of endocannabinoids in the encoding of task-relevant information by ensembles of hippocampal neurons under conditions in which the CB1 receptor antagonist, rimonabant, was administered during performance of a short-term memory delayed non-match to sample (DNMS) task in rats.

Objective

The influence of endocannabinoids on the encoding of task relevant information was determined via examination of the firing patterns of ensembles of CA1/CA3 hippocampal neurons during individual trials while rats performed a DNMS task.

Materials and methods

Multivariate discriminant analysis of the firing patterns of ensembles of hippocampal neurons was used to extract trial-specific codes for task-relevant information under different types of trial sequences.

Results

It was discovered that rimonabant blocked an inherent hippocampal memory encoding bias used by all animals. This bias was characterized as the preferential encoding of sample information on individual trials based on the similarity (i.e., same or different) and duration of the delay in the preceding trial.

Conclusions

The results indicate that endocannabinoids are a major influence on the strategic encoding biases of hippocampal ensembles and that pharmacological blockade of CB1 receptors facilitated performance by eliminating such influences.

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References

  • Alger BE (2002) Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog Neurobiol 68:247–286

    Article  PubMed  CAS  Google Scholar 

  • Beierlein M, Regehr WG (2006) Local interneurons regulate synaptic strength by retrograde release of endocannabinoids. J. Neurosci 26:9935–9943

    Article  PubMed  CAS  Google Scholar 

  • Cannich A, Wotjak CT, Kamprath K, Hermann H, Lutz B, Marsicano G (2004) CB1 cannabinoid receptors modulate kinase and phosphatase activity during extinction of conditioned fear in mice. Learn Mem 11:625–632

    Article  PubMed  Google Scholar 

  • Chevaleyre V, Castillo PE (2003) Heterosynaptic LTD of hippocampal GABAergic synapses: a novel role of endocannabinoids in regulating excitability. Neuron 38:461–472

    Article  PubMed  CAS  Google Scholar 

  • Cravatt BF, Lichtman AH (2004) The endogenous cannabinoid system and its role in nociceptive behavior. J Neurobiol 61:149–160

    Article  PubMed  CAS  Google Scholar 

  • Deadwyler SA, Bunn T, Hampson RE (1996) Hippocampal ensemble activity during spatial delayed-nonmatch-to-sample performance in rats. J Neurosci 16:354–372

    PubMed  CAS  Google Scholar 

  • Deadwyler SA, Hampson RE (2004) Differential but complementary mnemonic functions of the hippocampus and subiculum. Neuron 42:465–476

    Article  PubMed  CAS  Google Scholar 

  • Deadwyler SA, Goonawardena AV, Hampson RE (2007) Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes. Behav Pharm 18:571–580

    Article  CAS  Google Scholar 

  • Diana MA, Marty A (2004) Endocannabinoid-mediated short-term synaptic plasticity: depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE). Br J Pharmacol 142:9–19

    Article  PubMed  CAS  Google Scholar 

  • Edwards DA, Kim J, Alger BE (2006) Multiple mechanisms of endocannabinoid response inhibition in hippocampus. J Neurophysiol 95:67–75

    Article  PubMed  CAS  Google Scholar 

  • Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066

    PubMed  CAS  Google Scholar 

  • Gipson KE, Yeckel MF (2007) Coincident glutamatergic and cholinergic inputs transiently depress glutamate release at rat Schaffer collateral synapses. J Neurophysiol 97:4108–4119

    Article  PubMed  CAS  Google Scholar 

  • Hampson RE, Deadwyler SA (2000) Cannabinoids reveal the necessity of hippocampal neural encoding for short-term memory in rats. J Neurosci 20:8932–8942

    PubMed  CAS  Google Scholar 

  • Hampson RE, Simeral JD, Deadwyler SA (1999) Distribution of spatial and nonspatial information in dorsal hippocampus. Nature 402:610–614

    Article  PubMed  CAS  Google Scholar 

  • Hampson RE, Simeral JD, Deadwyler SA (2001) What ensemble recordings reveal about functional hippocampal cell encoding. Prog Brain Res 130:345–357

    Article  PubMed  CAS  Google Scholar 

  • Hampson RE, Simeral JD, Kelly EJ, Deadwyler SA (2003a) Tolerance to the memory disruptive effects of cannabinoids involves adaptation by hippocampal neurons. Hippocampus 13:543–556

    Article  PubMed  CAS  Google Scholar 

  • Hampson RE, Zhuang S-Y, Weiner JL, Deadwyler SA (2003b) Functional significance of cannabinoid-mediated, depolarization-induced suppression of inhibition (DSI) in the hippocampus. J Neurophysiol 90:55–64

    Article  PubMed  CAS  Google Scholar 

  • Hampson RE, Simeral J, Deadwyler SA (2005) Cognitive processes in replacement brain parts: a code for all reasons. In: Berger TW, Glanzman DL (eds) Toward replacement parts for the brain. MIT Press, Cambridge, pp 111–128

    Google Scholar 

  • Hashimotodani Y, Ohno-Shosaku T, Kano M (2007) Presynaptic monoacylglycerol lipase activity determines basal endocannabinoid tone and terminates retrograde endocannabinoid signaling in the hippocampus. J Neurosci 27:1211–1219

    Article  PubMed  CAS  Google Scholar 

  • Heyser CJ, Hampson RE, Deadwyler SA (1993) The effects of delta-9-THC on delayed match to sample performance in rats: alterations in short-term memory produced by changes in task specific firing of hippocampal neurons. J Pharmacol Exp Ther 264:294–307

    PubMed  CAS  Google Scholar 

  • Holter SM, Kallnik M, Wurst W, Marsicano G, Lutz B, Wotjak CT (2005) Cannabinoid CB1 receptor is dispensable for memory extinction in an appetitively-motivated learning task. Eur J Pharmacol 510:69–74

    Article  PubMed  CAS  Google Scholar 

  • Katona I, Urban GM, Wallace M, Ledent C, Jung K, Piomelli D, Mackie K, Freund TF (2006) Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci 26:5628–5637

    Article  PubMed  CAS  Google Scholar 

  • Kreitzer AC, Regehr WG (2002) Retrograde signaling by endocannabinoids. Curr Opin Neurobiol 12:324–330

    Article  PubMed  CAS  Google Scholar 

  • Laviolette SR, Grace AA (2006) Cannabinoids potentiate emotional learning plasticity in neurons of the medial prefrontal cortex through basolateral amygdala inputs. J Neurosci 26:6458–6468

    Article  PubMed  CAS  Google Scholar 

  • Marsicano G, Lutz B (2006) Neuromodulatory functions of the endocannabinoid system. J Endocrinol Invest 29:27–46

    PubMed  CAS  Google Scholar 

  • Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di M V, Lutz B (2002) The endogenous cannabinoid system controls extinction of aversive memories. Nature 418:530–534

    Article  PubMed  CAS  Google Scholar 

  • Meschler JP, Kraichely DM, Wilken GH, Howlett AC (2000) Inverse agonist properties of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR141716A) and 1-(2-chlorophenyl)-4-cyano-5-(4-methoxyphenyl)-1H-pyrazole-3-carboxyl ic acid phenylamide (CP-272871) for the CB(1) cannabinoid receptor. Biochem Pharmacol 60:1315–1323

    Article  PubMed  CAS  Google Scholar 

  • Pertwee RG (2005) Inverse agonism and neutral antagonism at cannabinoid CB1 receptors. Life Sci 76:1307–1324

    Article  PubMed  CAS  Google Scholar 

  • Rao CR (2002) Linear statistical inference and its applications. Wiley, New York, NY

    Google Scholar 

  • Safo PK, Cravatt BF, Regehr WG (2006) Retrograde endocannabinoid signaling in the cerebellar cortex. Cerebellum 5:134–145

    Article  PubMed  CAS  Google Scholar 

  • Simeral JD, Hampson RE, Deadwyler SA (2005) Behaviorally relevant neural codes in hippocampal ensembles: Detection on single trials. In: Baudry M, Bi X, Schreiber S (eds) Synaptic plasticity: from basic mechanisms to clinical applications. MIT Press, Cambridge, MA, pp 459–476

    Google Scholar 

  • Stevens J (2002) Applied multivariate statistics for the social sciences. Erlbaum, Hillsdale

    Google Scholar 

  • Varvel SA, Anum EA, Lichtman AH (2005) Disruption of CB(1) receptor signaling impairs extinction of spatial memory in mice. Psychopharmacology (Berl) 179:863–872

    Article  CAS  Google Scholar 

  • Vasquez C, Lewis DL (1999) The CB1 cannabinoid receptor can sequester G-proteins, making them unavailable to couple to other receptors. J Neurosci 19(21):9271–9280

    PubMed  CAS  Google Scholar 

  • Vasquez C, Navarro-Polanco RA, Huerta M, Trujillo X, Andrade F, Trujillo-Hernandez B, Hernandez L (2003) Effects of cannabinoids on endogenous K+ and Ca2+ currents in HEK293 cells. Can J Physiol Pharmacol 81(5):436–442

    Article  PubMed  CAS  Google Scholar 

  • Wilson RI, Nicoll RA (2001) Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 410:588–592

    Article  PubMed  CAS  Google Scholar 

  • Zangen A, Solinas M, Ikemoto S, Goldberg SR, Wise RA (2006) Two brain sites for cannabinoid reward. J Neurosci 26:4901–4907

    Article  PubMed  CAS  Google Scholar 

  • Zhuang S, Hampson RE, Deadwyler SA (2005) Behaviorally relevant endocannabinoid action in hippocampus: dependence on temporal summation of multiple inputs. Behav Pharmacol 16:463–471

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank the following for assistance with the project: David B. King, Wilson Davis, Nicholas Jones (University of Bath, UK), Lin Lin Ginzberg (University of Bath), Anushka V. Goonawardena, D. Lynn Johnson, Jason Locke, Joanne Konstantopoulos.

This work was supported by NIH grants MH613972 and DA08549 to R.E.H., and DA00119, DA07525 to S.A.D.

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Correspondence to Sam A. Deadwyler.

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Deadwyler, S.A., Hampson, R.E. Endocannabinoids modulate encoding of sequential memory in the rat hippocampus. Psychopharmacology 198, 577–586 (2008). https://doi.org/10.1007/s00213-007-1055-x

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  • DOI: https://doi.org/10.1007/s00213-007-1055-x

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