Perrier Lab

Our lab has a developed a strong expertise in the study of intrinsic properties of individual neurons.

Jean-Francois Perrier info

 

 

 

 

 

Credit: Gil Costa

Role of glial cells in motor control

We are investigating how glial cells from the spinal cord contribute to motor control. We discovered that astrocytes from the ventral horn of the spinal cord respond to endocannabinoids released from active neighbor interneurons. In turn, astrocytes release purines which inhibit the release of excitatory neurotransmitters. This cellular mechanism acts as a filter that prevents motor tremor. It also explains in part the anti-tremor effect of cannabis reported by patients suffering from neurodegenerative diseases. See Carlsen et al., Nature Neuroscience 2021.



Physiological function of neuronal intrinsic properties

Our lab has a developed a strong expertise in the study of intrinsic properties of individual neurons. By means of technique such as patch clamp recording, pharmacology, two-photon imaging in slice preparations from the central nervous, we are investigating how ion channels generate the electrical activity of neurons and how this contributes to the behavior of neural networks. Our recent results include:

- The identification of the first cellular mechanism responsible for the motor fatigue that occurs in the central nervous system. Motoneurons are the final common output of the central nervous system. Their synaptic activation triggers the contraction of the muscle they innervate. Neurons from the raphe nuclei in the brainstem release serotonin on motoneurons by means of synaptic contacts. Their activation facilitates the activity of motoneurons and thereby muscle contraction. During intense physical activity, serotonin release is increased. A spillover occurs and serotonin reaches extrasynaptic receptors located on the axon initial segment of motoneurons. This inhibits action potential genesis and thereby muscle contraction. In that way serotonin prevents excessive muscle contraction (Cotel et al., 2013).

                     






- The discovery of a new pathway that could prevent the development of temporal lobe epilepsy. The subiculum is a part of the temporal lope of the brain, and this is where temporal lobe epilepsy originates. Calcium flowing through CaV3 channels is responsible for the bursts of activity by pyramidal cells in the subiculum. When the activity of the neurons becomes overly synchronous, it results in abnormal electrical fluctuations, which lead to epileptic seizures. We have found that the activation of serotonin 2C receptors decreases the level of bursting by inhibiting CaV3 channels. This discovery could lead to the development of new principles for treating temporal lobe epilepsy (Petersen et al., 2017). See our popularization article in Videnskab.dk

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Publications in peer reviewed journals (lab members appear in bold)

59. Montalant A, Carlsen EMM, Perrier JF. Role of astrocytes in rhythmic motor activity. Physiol Rep. 2021 Sep;9(18):e15029

58. Magalhaes J, Ejlerskov P, Ering Hu E, Tresse E, Liu Y, Montalant A, Satriano L, Rundsten CF, Carlsen EM, Rydbirk R, Sharifi-Zarchi A, Andersen JB, Aznar S, Brudek T, Khodosevich K, Prinz M, Perrier JF, Sharma M, Gasser T, Marin A. PIAS2-mediated blockade of IFN-β signaling: A basis for sporadic Parkinson disease dementia. Mol Psychiatry. 2021 Jul 8. doi: 10.1038/s41380-021-01207.

57. Karadas M, Olsson C, Winther Hansen N, Perrier J-F, Webb JL, Huck A, Andersen UL and Thielscher A (2021) In-vitroRecordings of Neural Magnetic Activity From the Auditory Brainstem Using Color Centers in Diamond: A Simulation Study. Front. Neurosci.15:643614. 

56. Carlsen EM, Falk S, Skupio U, Robin L, Zottola AC, Marsicano G, Perrier JF. Spinal astroglial cannabinoid receptors control pathological tremor. Nature Neuroscience 2021 May;24(5):658-666.

55. Webb JL, Troise L, Hansen NW, Olsson C, Wojciechowski AM, Achard J, Brinza O, Staacke R, Kieschnick M, Meijer J, Thielscher A, Perrier JF, Berg-Sørensen K, Huck A, Andersen UL. Detection of biological signals from a live mammalian muscle using an early stage diamond quantum sensor. Sci Rep. 2021 Jan 28;11(1):2412. 

54. Webb JL, Troise L, Hansen NW, Achard J, Brinza O, Staacke R, Kieschnick M, Meijer J, Perrier J-F, Berg-Sørensen K, Huck A and Andersen UL (2020) Optimization of a Diamond Nitrogen Vacancy Centre Magnetometer for Sensing of Biological Signals. Front. Phys. 8:522536. doi: 10.3389/fphy.2020.522536

53. Sanz-Morello B, Pfisterer U, Winther Hansen N, Demharter S, Thakur A, Fujii K, Levitskii SA, Montalant A, Korshunova I, Mammen PP, Kamenski P, Noguchi S, Aldana BI, Hougaard KS, Perrier JF, Khodosevich K. Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function. EMBO J. 2020 Aug 3:e105759. doi: 10.15252/embj.2020105759

52. Carlsen E.M., Amrutkar D.V., Sandager K.N., Perrier, JF. (2019). Accurate and affordable assessment of physiological and pathological tremor in rodents with the accelerometer of a smartphone. J Neurophysiol. 122: 970–974, 2019.

51. Skov LJ, Ratner C, Hansen NW, Thompson JJ, Egerod KL, Burm H, Dalbøge LS, Hedegaard MA, Brakebusch C, Pers TH, Perrier JF, Holst B.. RhoA in tyrosine hydroxylase expressing neurons regulates food intake and body weight via altered sensitivity to peripheral hormones. J Neuroendocrinol. 2019 Jun 25. doi: 10.1111/jne.12761

50. Fitzpatrick CM, Runegaard AH, Christiansen SH, Jørgensen SH, Hansen NW, McGirr J, Sørensen AT, Perrier JF, Petersen A, Gether G, Woldbye DP, T Andreasen JT (2018). Differential effects of chemogenetic inhibition on dopamine and norepinephrine neurons in the mouse 5-choice serial reaction time task. Progress in Neuropsychopharmacology & Biological Psychiatry. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 2;90:264-276.

49. Perrier JF (2019). If serotonin does not exhaust you, it makes you stronger. J Physiol, 597(1):5-6.

48. Christensen RK, Delgado-Lezama R, Russo RE, Lind BL, Loeza-Alcocer E, Rath R, Fabbiani G, Schmitt N, Lauritzen M, Petersen AV, Carlsen EM, Perrier JF (2018). Spinal dorsal horn astrocytes release GABA in response to synaptic activation. J Physiol, 596(20):4983-4994.

47. Runegaard AH, Sørensen AT, Fitzpatrick CM, Jørgensen SH, Petersen A, Hansen NW, Weikop P, Andreasen JT, Mikkelsen JD, Perrier JF, Woldbye D, Rickhag M, Wortwein G and Gether U (2018). Locomotor- and reward-enhancing effects of cocaine are differentially regulated by chemogenetic stimulation of Gi-signaling in dopaminergic neurons. eNeuro, pii: ENEURO.0345-17.2018.

46. Perrier JF, Rasmussen H, Jørgensen, LK, Berg, RW (2018). Intense activity of the raphe spinal pathway depresses motor activity via a serotonin dependent mechanism. Front. Neural Circuits, 11:111. doi: 10.3389/fncir.2017.00111

45. von Schoubye NL, Frederiksen K, Kristiansen U, Petersen AV, Dalby NO, Morten Grunnet M, Jensen, HS, Jespersen T, Sohal VS, Perrier JF (2018). The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice. Neuroscience Letters, 662, 29-35.

44. Petersen A and Perrier JF (2017). La sérotonine prévient l’épilepsie du lobe temporal en inhibant les neurones à bouffée du subiculum. Médecine Sciences, 33(8-9):727-729.

43. Gjørlund MD, Carlsen EM, Kønig AB, Dmytrieva O, Petersen A, Jacobsen J, Berezin V, Perrier J and Jacobsen SO (2017). Soluble ectodomain of neuroligin 1 decreases synaptic activity by activating metabotropic glutamate receptor 2. Front. Mol. Neurosci. 10:116. doi: 10.3389/fnmol.2017.00116

42. Petersen A, Jensen CS, Crépel V, Falkerslev M and Perrier JF (2017). Serotonin regulates the firing of principal cells of the subiculum by inhibiting a T-type Ca2+ current. Front. Cell. Neurosci. 11:60. doi: 10.3389/fncel.2017.00060

41. D'Amico JM, Annie A Butler AA, Heroux ME, Cotel F, Perrier JF, Butler J, Gandevia SC, and Janet L Taylor JL (2017). Human Motoneurone Excitability is Depressed by Activation of 5HT1A Receptors with Buspirone". J Physiol, 595, 1763-1773.

40. Carlsen EM, Rasmussen R. (2017). Bursting deep dorsal horn neurons: the pharmacological target for the antispastic effects of zolmitriptan? J Neurophysiol.;117(5):1841-1843.

39. Carlsen EM, Rasmussen R. (2017). Protein Networks in Alzheimer's Disease. Cell Syst. 4(2):153-155.

38. Rasmussen R, Carlsen EM. (2017). Motor cortical HCN channels: a contributor to coordinated forelimb movements in rodents? J Physiol. 595(3):633-634.

37. Petersen AV, Cotel F, Perrier JF (2017). Plasticity of the axon initial segment:  Fast and slow processes with multiple functional roles. The Neuroscientist, Volume: 23 issue: 4, page(s): 364-373.
Frontpage of The NeuroScientist

36. Rasmussen R, Carlsen EM. (2016). Spontaneous Functional Recovery from Incomplete Spinal Cord Injury. J Neurosci. 17;36(33):8535-7.

35. Perrier JF (2016). Modulation of motoneuron activity by serotonin. Dan Med J 2016:63(2);B5204

34. Benned-Jensen T, Christensen RK, Denti F, Perrier JF, Rasmussen H, and Olesen SP (2016). Live imaging of Kv7.2/7.3 cell surface dynamics at the axon initial segment: high steady state stability and calpain-dependent excitotoxic downregulation revealed. Journal of Neurosciences, 2631-15.

33. Petersen AV, Johansen EØ and Perrier J-F (2015) Fast and reliable identification of axons, axon initial segments and dendrites with local field potential recording. Front. Cell. Neurosci. 9:429

32. Korshunova Irina, Gjørlund MD, Owczarek S, Petersen AV, Perrier JF, Gøtzsche CR, Berezin V (2015). A neuroligin-1 derived peptide stimulates phosphorylation of the NMDA receptor subunit NR1 and rescues an MK-801 - induced decrease in LTP and memory impairment. Pharmacology Research & Perspectives, 3 (2) 1-12.

31. Perrier JF, Cotel F (2015). Serotonergic modulation of spinal motor control. Current Opinion of Neurobiology, 33: 1-7.

30. Carlsen EM, Perrier JF (2014). Purines released from astrocytes inhibit excitatory synaptic transmission in the ventral horn of the spinal cord. Front. Neural Circuits 8:60.

29. Christensen RK, Petersen AV, Schmitt N, Perrier JF (2014). Fast detection of extrasynaptic GABA with a whole-cell sniffer. Front. Cell. Neurosci. 8, 133.

28. Perrier JF (2013) Encadrement de l’excitabilité des motoneurones par la sérotonine. Médecine Sciences 29-6: 564-566.

27. Cotel F, Exley R, Cragg SJ, Perrier JF (2013) Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation. Proceedings of the National Academy of Sciences of the United States of America 110:4774-4779.

26. Perrier JF, Rasmussen HB, Christensen RK, Petersen AV (2013) Modulation of the intrinsic properties of motoneurons by serotonin. Current pharmaceutical design 19: 4371-4384.

25. Christensen RK, Petersen AV, Perrier JF (2013) How do glial cells contribute to motor control? Current pharmaceutical design 19: 4385-4399.

24. Munch AS, Smith M, Moldovan M, Perrier JF (2010) Visual patch clamp recording of neurons in thick portions of the adult spinal cord. J Neurosci Methods 190:205-213.

23. Perrier JF, Cotel F (2008) Serotonin differentially modulates the intrinsic properties of spinal motoneurons from the adult turtle. J Physiol 586:1233-1238.

22. Smith M, Perrier JF (2006) Intrinsic properties shape the firing pattern of ventral horn interneurons from the spinal cord of the adult turtle. J Neurophysiol 96:2670-2677.

21. Perrier JF, Tresch MC (2005) Recruitment of motor neuronal persistent inward currents shapes withdrawal reflexes in the frog. J Physiol 562:507-520.

20. Perrier JF, Delgado-Lezama R (2005) Synaptic release of serotonin induced by stimulation of the raphe nucleus promotes plateau potentials in spinal motoneurons of the adult turtle. J Neurosci 25:7993-7999.

19. Grunnet M, Jespersen T, Perrier JF (2004) 5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels. J Neurosci Res 78:845-854.

18. Simon M, Perrier JF, Hounsgaard J (2003) Subcellular distribution of L-type Ca2+ channels responsible for plateau potentials in motoneurons from the lumbar spinal cord of the turtle. Eur J Neurosci 18:258-266.

17. Perrier JF, Hounsgaard J (2003) 5-HT2 receptors promote plateau potentials in turtle spinal motoneurons by facilitating an L-type calcium current. J Neurophysiol 89:954-959.

16. Perrier JF, Alaburda A, Hounsgaard J (2003) 5-HT1A receptors increase excitability of spinal motoneurons by inhibiting a TASK-1-like K+ current in the adult turtle. J Physiol 548:485-492.

15. Perrier JF, Alaburda A, Hounsgaard J (2002) Spinal plasticity mediated by postsynaptic L-type Ca2+ channels. Brain Res Brain Res Rev 40:223-229.

14. Alaburda A, Perrier JF, Hounsgaard J (2002) Mechanisms causing plateau potentials in spinal motoneurones. Adv Exp Med Biol 508:219-226.

13. Alaburda A, Perrier JF, Hounsgaard J (2002) An M-like outward current regulates the excitability of spinal motoneurones in the adult turtle. J Physiol 540:875-881.

12. Perrier JF, Noraberg J, Simon M, Hounsgaard J (2000) Dedifferentiation of intrinsic response properties of motoneurons in organotypic cultures of the spinal cord of the adult turtle. Eur J Neurosci 12:2397-2404.

11. Perrier JF, Mejia-Gervacio S, Hounsgaard J (2000) Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin. J Physiol 528 Pt 1:107-113.

10. Perrier JF, Hounsgaard J (2000) Development and regulation of response properties in spinal cord motoneurons. Brain Res Bull 53:529-535.

9. Perrier JF, D'Incamps BL, Kouchtir-Devanne N, Jami L, Zytnicki D (2000) Cooperation of muscle and cutaneous afferents in the feedback of contraction to peroneal motoneurons. J Neurophysiol 83:3201-3208.

8. Perrier JF, D'Incamps BL, Kouchtir-Devanne N, Jami L, Zytnicki D (2000) Effects on peroneal motoneurons of cutaneous afferents activated by mechanical or electrical stimulations. J Neurophysiol 83:3209-3216.

7. Perrier JF, Hounsgaard J (1999) Ca(2+)-activated nonselective cationic current (I(CAN)) in turtle motoneurons. J Neurophysiol 82:730-735.

6. Delgado-Lezama R, Perrier JF, Hounsgaard J (1999) Local facilitation of plateau potentials in dendrites of turtle motoneurones by synaptic activation of metabotropic receptors. J Physiol 515 ( Pt 1):203-207.

5. Delgado-Lezama R, Perrier JF, Hounsgaard J (1999) Oscillatory interaction between dorsal root excitability and dorsal root potentials in the spinal cord of the turtle. Neuroscience 93:731-739.

4. Kouchtir N, Destombes J, Perrier JF, Horcholle-Bossavit G, Jami L (1997) Short-latency synaptic patterns among cat peroneal motoneurons. Brain Res 774:159-166.

3. Delgado-Lezama R, Perrier JF, Nedergaard S, Svirskis G, Hounsgaard J (1997) Metabotropic synaptic regulation of intrinsic response properties of turtle spinal motoneurones. J Physiol 504 ( Pt 1):97-102.

2. Zytnicki D, Lafleur J, Kouchtir N, Perrier JF (1995) Heterogeneity of contraction-induced effects in neurons of the cat dorsal spinocerebellar tract. J Physiol 487 ( Pt 3):761-772.

1. Kouchtir N, Perrier JF, Zytnicki D, Jami L (1995) Contraction-induced excitation in cat peroneal motoneurons. J Neurophysiol 73:974-982.

 

 

Master’s project in Neuroscience

We are offering Master’s thesis project in neuronal calcium imaging and electrophysiology to study the role of interneurons in an animal model of schizophrenia.

The project will start in September or as soon as possible hereafter. We are looking for a candidate with a Master’s project duration of 12-18 months.

Project description

Parvalbumin-positive (PV+) interneurons comprise a third of total inhibitory neuron population in the cortex and were shown to be the key subtype of interneurons that control information flow. PV+ interneurons regulate synchronization of oscillations (i.e. rhythmic brain activity) in the brain by controlling output of principal neurons and thus modulate cortical network activity. PV+ interneurons are affected in schizophrenia disorders. However, there are >10 subtypes of PV+ interneurons and it is unknown what subtypes are impaired in schizophrenia and contribute to brain dysfunction.

To identify subtypes of PV+ interneurons that are impaired in schizophrenia, we will implement 15q11.3 microdeletion mice, which exhibit schizophrenia-like behavior and will cross them with PV-Cre mice, such that Cre recombinase is expressed only on PV+ neurons. We will inject these mice with AAV-FLEX-GCaMP6s virus into the cortex resulting in the expression of the calcium indicator GCaMP6s, exclusively in PV+ neurons.

We will then assess the activity PV+ interneurons by means of calcium imaging technique in wild type and 15q13.3 mice. After the imaging, we will fix the sections and label by immunohistochemistry several subtype-specific markers of PV+ neurons. Since we will know activity for each PV+ neuron from calcium imaging and their subtype from immunohistochemistry, we will analyze how activity of each PV+ neuron subtype is affected in schizophrenia model and will identify those that have most dramatic changes, thus likely having the largest contribution to schizophrenia phenotype.

Methods: calcium imaging and electrophysiology in a slice preparation of the brain.

Scientific environment

The project is a collaboration between the labs of Konstantin Khodosevich (BRIC, UCPH) and Jean-François Perrier (Department of Neuroscience, UCPH). The candidate will be work under the daily supervision of Nikolaj Winther Hansen at the Department of Neuroscience (Mærsk Tower, Blegdamsvej 3, Copenhagen).

Your qualifications: You are highly motivated and studying Neuroscience, MedTek, KBS, Human Biology, Molecular Biomedicine. You are flexible, ambitious and can work independently.

Application 

Contact Jean-François Perrier (perrier@sund.ku.dk) including a CV and grade transcript.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Lab members

Name Title Job responsibilities Image
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Alexia Montalant PhD Student Perrier lab Billede af Alexia Montalant
Altair Brito dos Santos Postdoc Perrier lab Billede af Altair Brito dos Santos
Anne Marie Nordvig Petersen Laboratory Technician Perrier Lab Billede af Anne Marie Nordvig Petersen
Jean-Francois Marie Perrier Associate Professor Perrier lab Billede af Jean-Francois Marie Perrier
Jørn Dybkjær Hounsgaard No job title VIP Perrier Lab Billede af Jørn Dybkjær Hounsgaard
Liangchen Guo Academic Research Staff Billede af Liangchen Guo
Nikolaj Winther Hansen PhD Student Perrier lab Billede af Nikolaj Winther Hansen
Silas Dalum Larsen Laboratory Assistant Perrier Lab Billede af Silas Dalum Larsen
Thor Linnet Academic Research Staff Sørensen Lab Billede af Thor Linnet

Collaborations