Skip to main content
SpringerLink
Log in

Amygdala electrical stimulation for operant conditioning in rat navigation

  • Original Article
  • Published:
Biomedical Engineering Letters Aims and scope Submit manuscript

Abstract

There have been several attempts to navigate the locomotion of animals by neuromodulation. The most common method is animal training with electrical brain stimulation for directional cues and rewards; the basic principle is to activate dopamine-mediated neural reward pathways such as the medial forebrain bundle (MFB) when the animal correctly follows the external commands. In this study, the amygdala, which is the brain region responsible for fear modulation, was targeted for punishment training. The brain regions of MFB, amygdala, and barrel cortex were electrically stimulated for reward, punishment, and directional cues, respectively. Electrical stimulation was applied to the amygdala of rats when they failed to follow directional commands. First, two different amygdala regions, i.e., basolateral amygdala (BLA) and central amygdala (CeA), were stimulated and compared in terms of behavior responses, success and correction rates for training, and gene expression for learning and memory. Then, the training was performed in three groups: group R (MFB stimulation for reward), group P (BLA stimulation for punishment), and group RP (both MFB and BLA stimulation for reward and punishment). In group P, after the training, RNA sequencing was conducted to detect gene expression and demonstrate the effect of punishment learning. Group P showed higher success rates than group R, and group RP exhibited the most effective locomotion control among the three groups. Gene expression results imply that BLA stimulation can be more effective as a punishment in the learning process than CeA stimulation. We developed a new method to navigate rat locomotion behaviors by applying amygdala stimulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Talwar SK, Xu S, Hawley ES, Weiss SA, Moxon KA, Chapin JK. Rat navigation guided by remote control. Nature. 2002;417(6884):37–8.

    Article  CAS  PubMed  ADS  Google Scholar 

  2. Lee MG, et al. Operant conditioning of rat navigation using electrical stimulation for directional cues and rewards. Behav Process. 2010;84(3):715–20.

    Article  Google Scholar 

  3. Ahmadi A, et al. Rat navigation by stimulating somatosensory cortex. J Bionic Eng. 2019;16(5):931–42.

    Article  Google Scholar 

  4. Sato H, et al. Remote radio control of insect flight. Front Integr Neurosci. 2009;3:24.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Van Truong T, et al. Flight behavior of the rhinoceros beetle Trypoxylus dichotomus during electrical nerve stimulation. Bioinspir Biomim. 2012;7(3):036021.

    Article  PubMed  ADS  Google Scholar 

  6. Choo HY, et al. Electrical stimulation of coleopteran muscle for initiating flight. PLoS ONE. 2016;11(4):e0151808.

    Article  MathSciNet  PubMed  PubMed Central  Google Scholar 

  7. Martin JP, et al. Central-complex control of movement in the freely walking cockroach. Curr Biol. 2015;25(21):2795–803.

    Article  CAS  PubMed  Google Scholar 

  8. Erickson JC, et al. Effective stimulus parameters for directed locomotion in Madagascar hissing cockroach biobot. PLoS ONE. 2015;10(8):e0134348.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Johnsen PB, Teeter JH. Behavioral responses of bonnethead sharks (Sphyrna tiburo) to controlled olfactory stimulation. Mar Freshw Behav Phy. 1985;11(4):283–91.

    Google Scholar 

  10. Gardiner JM, Atema J. The function of bilateral odor arrival time differences in olfactory orientation of sharks. Curr Biol. 2010;20(13):1187–91.

    Article  CAS  PubMed  Google Scholar 

  11. Cai L, et al. Modulating motor behaviors by electrical stimulation of specific nuclei in pigeons. J Bionic Eng. 2015;12(4):555–64.

    Article  Google Scholar 

  12. Shim S, et al. A handheld neural stimulation controller for avian navigation guided by remote control. Biomed Mater Eng. 2020;30(5–6):497–507.

    PubMed  Google Scholar 

  13. Huai RT, Yang JQ, Wang H. The robo-pigeon based on the multiple brain regions synchronization implanted microelectrodes. Bioengineered. 2016;7(4):213–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hasselmo ME, et al. Neuromodulation, theta rhythm and rat spatial navigation. Neural Netw. 2002;15(4):689–707.

    Article  PubMed  Google Scholar 

  15. Khajei S, Shalchyan V, Daliri MR. Ratbot navigation using deep brain stimulation in ventral posteromedial nucleus. Bioengineered. 2019;10(1):250–60.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Yu Y, et al. Automatic training of rat cyborgs for navigation. Comput Intell Neurosci. 2016;2016:6459251.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Xu K, et al. A novel turning behavior control method for rat-robot through the stimulation of ventral posteromedial thalamic nucleus. Behav Brain Res. 2016;298(Pt B):150–7.

    Article  PubMed  ADS  Google Scholar 

  18. Chen X, Xu K, Ye S, Guo S, Zheng X. A remote constant current stimulator designed for rat-robot navigation. 2013.

  19. Ambroggi F, et al. Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons. Neuron. 2008;59(4):648–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chen S, et al. Optogenetics based rat-robot control: optical stimulation encodes “stop” and “escape” commands. Ann Biomed Eng. 2015;43(8):1851–64.

    Article  PubMed  Google Scholar 

  21. Huai R, et al. A new robo-animals navigation method guided by the remote control. In: 2009 2nd international conference on biomedical engineering and informatics. 2009. IEEE.

  22. Zhang C, Sun C, Gao L, Zheng N, Chen W, Zheng X. Bio-robots automatic navigation with graded electric reward stimulation based on reinforcement learning. 2013.

  23. Kamprath K, Wotjak CT. Nonassociative learning processes determine expression and extinction of conditioned fear in mice. Learn Mem. 2004;11(6):770–86.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Baldi E, Lorenzini CA, Bucherelli C. Footshock intensity and generalization in contextual and auditory-cued fear conditioning in the rat. Neurobiol Learn Mem. 2004;81(3):162–6.

    Article  PubMed  Google Scholar 

  25. Haluk DM, Wickman K. Evaluation of study design variables and their impact on food-maintained operant responding in mice. Behav Brain Res. 2010;207(2):394–401.

    Article  PubMed  Google Scholar 

  26. Guo ZV, et al. Procedures for behavioral experiments in head-fixed mice. PLoS ONE. 2014;9(2):e88678.

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  27. Rostron CL, et al. Instrumental conditioning for food reinforcement in the spontaneously hypertensive rat model of attention deficit hyperactivity disorder. BMC Res Notes. 2017;10(1):525.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kong C, et al. Optimization of medial forebrain bundle stimulation parameters for operant conditioning of rats. Stereotact Funct Neurosurg. 2019;97(1):1–9.

    Article  PubMed  Google Scholar 

  29. Kim H, et al. Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters. Brain Stimul. 2014;7(5):748–56.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Senova S, et al. Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues. Sci Rep. 2017;7(1):43997.

    Article  PubMed  ADS  Google Scholar 

  31. O’Connor DH, et al. Neural coding during active somatosensation revealed using illusory touch. Nat Neurosci. 2013;16(7):958–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Arabzadeh E, Petersen RS, Diamond ME. Encoding of whisker vibration by rat barrel cortex neurons: implications for texture discrimination. J Neurosci. 2003;23(27):9146–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Meyer ME, Meyer ME. The effects of bilateral and unilateral vibrissotomy on behavior within aquatic and terrestrial environments. Physiol Behav. 1992;51(4):877–80.

    Article  CAS  PubMed  Google Scholar 

  34. Shuler MG, Krupa DJ, Nicolelis MA. Bilateral integration of whisker information in the primary somatosensory cortex of rats. J Neurosci. 2001;21(14):5251–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lalumiere RT. Optogenetic dissection of amygdala functioning. Front Behav Neurosci. 2014;8:107.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ehrlich I, et al. Amygdala inhibitory circuits and the control of fear memory. Neuron. 2009;62(6):757–71.

    Article  CAS  PubMed  Google Scholar 

  37. Amano T, et al. The fear circuit revisited: contributions of the basal amygdala nuclei to conditioned fear. J Neurosci. 2011;31(43):15481–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Aggleton J. A description of intra-amygdaloid connections in old world monkeys. Exp Brain Res. 1985;57(2):390–9.

    Article  CAS  PubMed  Google Scholar 

  39. De Ridder D, Vanneste S. Burst and tonic spinal cord stimulation: different and common brain mechanisms. Neuromodulation. 2016;19(1):47–59.

    Article  PubMed  Google Scholar 

  40. Ikemoto S, Panksepp J. The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking. Brain Res Rev. 1999;31(1):6–41.

    Article  CAS  PubMed  Google Scholar 

  41. Gage GJ, Kipke DR, Shain W. Whole animal perfusion fixation for rodents. J Vis Exp. 2012;65:e3564.

    Google Scholar 

  42. Bullitt E. Expression of C-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol. 1990;296(4):517–30.

    Article  CAS  PubMed  Google Scholar 

  43. Jain N, et al. Local-pooled-error test for identifying differentially expressed genes with a small number of replicated microarrays. Bioinformatics. 2003;19(15):1945–51.

    Article  CAS  PubMed  Google Scholar 

  44. Arikawa E, et al. Cross-platform comparison of SYBR green real-time PCR with TaqMan PCR, microarrays and other gene expression measurement technologies evaluated in the microarray quality control (MAQC) study. BMC Genom. 2008;9:328.

    Article  Google Scholar 

  45. Chen DY, et al. A critical role for IGF-II in memory consolidation and enhancement. Nature. 2011;469(7331):491–7.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  46. Stern SA, et al. Enhancement of memories by systemic administration of insulin-like growth factor II. Neuropsychopharmacology. 2014;39(9):2179–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pascual-Lucas M, et al. Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice. EMBO Mol Med. 2014;6(10):1246–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Friling S, et al. Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells. Proc Natl Acad Sci USA. 2009;106(18):7613–8.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  49. Bellander M, et al. Preliminary evidence that allelic variation in the LMX1A gene influences training-related working memory improvement. Neuropsychologia. 2011;49(7):1938–42.

    Article  PubMed  Google Scholar 

  50. Nakamura E, et al. Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour. Genes Cells. 1998;3(12):811–22.

    Article  CAS  PubMed  Google Scholar 

  51. Viggiano A, et al. Anxiety as a neurodevelopmental disorder in a neuronal subpopulation: evidence from gene expression data. Psychiatry Res. 2015;228(3):729–40.

    Article  PubMed  Google Scholar 

  52. Uchino S, et al. Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. J Neurochem. 2006;97(4):1203–14.

    Article  CAS  PubMed  Google Scholar 

  53. Naisbitt S, et al. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron. 1999;23(3):569–82.

    Article  CAS  PubMed  Google Scholar 

  54. Uppal N, et al. Ultrastructural analyses in the hippocampus CA1 field in Shank3-deficient mice. Mol Autism. 2015;6:41.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Bey AL, et al. Brain region-specific disruption of shank3 in mice reveals a dissociation for cortical and striatal circuits in autism-related behaviors. Transl Psychiatry. 2018;8(1):94.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Amengual J, et al. STRA6 is critical for cellular vitamin A uptake and homeostasis. Hum Mol Genet. 2014;23(20):5402–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Moresi V, et al. Chapter 18—Epigenetics of muscle disorders. In: Tollefsbol TO, editor., et al., Medical epigenetics. Boston: Academic Press; 2016. p. 315–33.

    Chapter  Google Scholar 

  58. Cai H, et al. Central amygdala PKC-δ+ neurons mediate the influence of multiple anorexigenic signals. Nat Neurosci. 2014;17(9):1240–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Felix-Ortiz AC, et al. BLA to vHPC inputs modulate anxiety-related behaviors. Neuron. 2013;79(4):658–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Tye KM, et al. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature. 2011;471(7338):358–62.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  61. Sergio L, et al. The amygdala and anxiety, In: Barbara F, editor. The amygdala, IntechOpen: Rijeka. 2017. p. Ch. 7.

  62. Wall NR, et al. Monosynaptic circuit tracing in vivo through cre-dependent targeting and complementation of modified rabies virus. Proc Natl Acad Sci. 2010;107(50):21848–53.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  63. LeDoux J. The emotional brain, fear, and the amygdala. Cell Mol Neurobiol. 2003;23(4–5):727–38.

    Article  PubMed  Google Scholar 

  64. Gao YJ, et al. Contributions of the anterior cingulate cortex and amygdala to pain- and fear-conditioned place avoidance in rats. Pain. 2004;110(1–2):343–53.

    Article  PubMed  Google Scholar 

  65. Tanimoto S, et al. Differential contributions of the basolateral and central nuclei of the amygdala in the negative affective component of chemical somatic and visceral pains in rats. Eur J Neurosci. 2003;18(8):2343–50.

    Article  PubMed  Google Scholar 

  66. Tran L, Greenwood-Van Meerveld B. Lateralized amygdala activation: importance in the regulation of anxiety and pain behavior. Physiol Behav. 2012;105(2):371–5.

    Article  CAS  PubMed  Google Scholar 

  67. Johnson AC, Greenwood-Van Meerveld B. Central amygdala mechanisms regulating visceral pain. Psychoneuroendocrinology. 2015;61:8.

    Article  Google Scholar 

  68. Johnson AC, Greenwood-Van Meerveld B. Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat. Neuropharmacology. 2015;93:116–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Everitt B, Cador M, Robbins T. Interactions between the amygdala and ventral striatum in stimulus-reward associations: studies using a second-order schedule of sexual reinforcement. Neuroscience. 1989;30(1):63–75.

    Article  CAS  PubMed  Google Scholar 

  70. Gallagher M, Graham PW, Holland PC. The amygdala central nucleus and appetitive Pavlovian conditioning: lesions impair one class of conditioned behavior. J Neurosci. 1990;10(6):1906–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hatfield T, et al. Neurotoxic lesions of basolateral, but not central, amygdala interfere with Pavlovian second-order conditioning and reinforcer devaluation effects. J Neurosci. 1996;16(16):5256–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hiroi N, White NM. The lateral nucleus of the amygdala mediates expression of the amphetamine-produced conditioned place preference. J Neurosci. 1991;11(7):2107–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. McDonald RJ, White NM. A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum. 2013.

  74. Clem RL, Huganir RL. Calcium-permeable AMPA receptor dynamics mediate fear memory erasure. Science. 2010;330(6007):1108–12.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  75. Johansen JP, et al. Optical activation of lateral amygdala pyramidal cells instructs associative fear learning. Proc Natl Acad Sci. 2010;107(28):12692–7.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  76. Tye KM, et al. Rapid strengthening of thalamo-amygdala synapses mediates cue–reward learning. Nature. 2008;453(7199):1253–7.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  77. Kaczmarek L. Gene expression in learning processes. Acta Neurobiol Exp (Wars). 2000;60(3):419–24.

    Article  CAS  PubMed  Google Scholar 

  78. Martinez JL, Thompson KJ, Sikorski AM. Chapter 4—Gene expression in learning and memory. In: Kesner RP, Martinez JL, editors. Neurobiology of learning and memory (Second Edition). Burlington: Academic Press; 2007. p. 129–53.

    Chapter  Google Scholar 

  79. Yang Y, Wang JZ. From structure to behavior in basolateral amygdala-hippocampus circuits. Front Neural Circuits. 2017;11:86.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Akirav I, Richter-Levin G. Biphasic modulation of hippocampal plasticity by behavioral stress and basolateral amygdala stimulation in the rat. J Neurosci. 1999;19(23):10530–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Akirav I, Sandi C, Richter-Levin G. Differential activation of hippocampus and amygdala following spatial learning under stress. Eur J Neurosci. 2001;14(4):719–25.

    Article  CAS  PubMed  Google Scholar 

  82. Maren S, Phan KL, Liberzon I. The contextual brain: implications for fear conditioning, extinction and psychopathology. Nat Rev Neurosci. 2013;14(6):417–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bijanki KR, et al. Case report: stimulation of the right amygdala induces transient changes in affective bias. Brain Stimul. 2014;7(5):690–3.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Lanteaume L, et al. Emotion induction after direct intracerebral stimulations of human amygdala. Cereb Cortex. 2007;17(6):1307–13.

    Article  PubMed  Google Scholar 

  85. McDONALD AJ. Cytoarchitecture of the central amygdaloid nucleus of the rat. J Comp Neurol. 1982;208(4):401–18.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by Convergent Technology R&D Program for Human Augmentation and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2019M3C1B8090805), Basic Science Research Program through the NRF funded by the Ministry of Education (NRF-2022R1I1A4063209, NRF-2022R1A2C2005062), and Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (No.RS-2022-00150000, Artificial Intelligence Convergence Innovation Human Resources Development (Ewha Womans University)). This work was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Korea (grant number: HI20C0954).

Author information

Authors and Affiliations

  1. Department of Electronic and Electrical Engineering, Ewha Womans University, Seoul, 03760, Republic of Korea

    Youjin Lee, Yoon Kyung Cho & Sang Beom Jun

  2. Graduate Program in Smart Factory, Ewha Womans University, Seoul, 03760, Republic of Korea

    Youjin Lee & Sang Beom Jun

  3. Department of Electrical and Computer Engineering, Rice University, Houston, TX, 77005, USA

    Soonyoung Kim

  4. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Chanho Kong & Jin Woo Chang

  5. Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Jin Woo Chang

  6. Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea

    Sang Beom Jun

Authors
  1. Youjin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soonyoung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoon Kyung Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chanho Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jin Woo Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sang Beom Jun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YL: Conceptualization, Data curation, Formal analysis, Investigation, Visualization, Methodology, Writing—original draft. SK: Investigation, Methodology. YKC: Investigation, Methodology. CK: Investigation, Methodology. JWC: Conceptualization, Supervision, Funding acquisition, Project administration. SBJ: Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Project administration, Writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Sang Beom Jun.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, Y., Kim, S., Cho, Y.K. et al. Amygdala electrical stimulation for operant conditioning in rat navigation. Biomed. Eng. Lett. 14, 291–306 (2024). https://doi.org/10.1007/s13534-023-00336-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13534-023-00336-1

Keywords

Search

Navigation