Comparison of evoked synaptic responses and synaptic plasticity at Schaffer collateral-CA1 and perforant path-CA1 synapses in freely behaving adult rats [Elektronische Ressource] / by Ayla Aksoy Aksel

Aksoy-Aksel, Ayla

Sujets

• Gesundheit

Informations

• Publié par: ruhr-universitat_bochum
• Publié le: 01 janvier 2010
• Nombre de lectures: 10
• Langue: English
• Poids de l'ouvrage: 4 Mo

Extrait

COMPARISON OF EVOKED SYNAPTIC RESPONSES AND SYNAPTIC
PLASTICITY AT SCHAFFER COLLATERAL–CA1 AND PERFORANT PATH-
CA1 SYNAPSES IN FREELY BEHAVING ADULT RATS
by
Ayla Aksoy Aksel
A thesis submitted in partial fulfillment of the requirements for the degree of
Philosophiae Doctoris (PhD) in Neuroscience
of the International Graduate School of Neuroscience
Ruhr University Bochum


stJuly 31 2010

This  research  was  conducted  at   the  Department  of  Experimental  Neurophysiology,      
within  the  Medical  Faculty  of  the  Ruh r  University      
under  the  supervision  of  Prof.  Dr.  Denise  Manahan -­‐Vaughan.
 
Printed  with  the  permission  of  the  International  Graduate  School  of  Neuroscience,  Ruhr  
University  Bochum  


Statement

I certify herewith that the dissertation at hand was completed and written independently and
without outside assistance. The "Guidelines for Good Scientific Practice" according to § 9, Sec. 3
were adhered to. This work has never been submitted in this or a similar form at this or any other
domestic or foreign institution of higher learning as a dissertation.



Ayla Aksoy Aksel

Bochum, 31.08.2010









2
PhD  Commission  

Chair:  
 
st1    Internal  Examiner:  Prof.  Dr.  Denise  Manahan -­‐Vaughan  
 
nd2  Internal  Examiner:   PD  Dr.  Boris  Suchan  
 
External  Examiner:    
 
Non -­‐Specialist:  



 
 
Date  of  Final  Examination:  
PhD  Grade  Assigned:  
3

TABLE of CONTENTS

I. List of Figures ..................................................................... ...................................................... 8
II. List of Abbreviations.............................................................................. 11
III.List of Compounds................................................. 13
IV.Abstract................................................................................................................................... 14
1 Introduction............................ 15
1.1 The anatomy of the hippocampus ........................................................................................... 15
1.1.1 The anatomy of the CA1 sub-region................. 17
1.2 The hippocampus and learning and memory .......................................................................... 19
1.2.1 The CA1 sub-region and learning and memory 20
1.3 Synaptic plasticity ................................................................................................................... 21
1.3.1 Long-term potentiation...................................................................................................... 22
1.3.2 Long-term depression........ 23
1.3.3 Synaptic plasticity in the CA1 sub-region......................................................................... 23
1.3.3.1 Synaptic plasticity in the Schaffer Collateral-CA1 synapse.... 23
1.3.3.2 Synaptic plasticity in the perforant path-CA1 synapse ............................................ 24
1.4 Glutamate receptors in the CA1 region................................................... 26
4
1.4.1 The ionotropic glutamate receptors: AMPA and NMDA ................................................. 26
1.4.2 The metabotropic glutamate receptors .............................................. 27
1.5 Learning-facilitated plasticity ................................................................................................. 28
1.6 Aim of this study ..................................................................................................................... 29
2. Materials and Methods ........................................................................................................... 30
2.1 Laboratory Animals................. 30
2.2 Electrodes ................................................................................................................................ 30
2.3 Electrode implantation ............................................................................................................ 31
2.3.1 Anesthesia and surgical preparation.................. 31
2.3.2 Electrophysiologically-guided electrode insertion............................................................ 32
2.4 Electrophysiological recordings.............................................................. 33
2.4.1 Experimental set-up........................................................................................................... 33
2.4.2 Recordings of basal synaptic transmission and induction of synaptic plasticity .............. 34
2.4.3 Analysis of evoked potentials ........................................................................................... 36
2.4.4 Severance of the Schaffer collateral input......................................................................... 36
2.5 Drug treatment......................................................................................................................... 37
2.5.1 Administration................... 37
2.5.2 Compounds........................................................................................................................ 38
2.6 Behavioural experiments......................................................................................................... 38
2.6.1 Novel holeboard and object-place constellations.............................. 38
2.6.2 Simultaneous electrophysiological recordings during spatial learning............................. 39
5
2.7 Histological analysis ............................................................................................................... 40
2.8 Data Analysis.......................... 40
3. Results ...................................................................................................................................... 41
3.1 Establishment of electrophysiological procedures for recordings of pp-CA1 potentials in
freely behaving rats ................................................................................................................ 41
3.2 Characteristics of pp-CA1 potentials: comparison with SC-CA1 potentials .......................... 46
3.3 Synaptic transmission and plasticity at pp-CA1 and SC-CA1 synapses................................. 50
3.3.1 Ultra short-term plasticity ................................................................. 50
3.3.2 The effects of high-frequency stimulation on the pp-CA1 synapse ................................. 53
3.3.3 The effects of low-frequency stimulation on the pp-CA1 synapse... 56
3.4 Effect of severance of the Schaffer collaterals on the synaptic strength of the pp-CA1
synapse .................................................................................................................................. 59
3.4.1 The effects of high-frequency stimulation on the pp-CA1 synapse under intact
conditions and following severance of the Schaffer collaterals ............................................ 59
3.4.2 The effects of low-frequency stimulation on the pp-CA1 synapse under intact conditions
and following severance of the Schaffer collaterals .............................................................. 62
3.5 Pharmacological investigations on the basal synaptic transmission and synaptic plasticity of
the pp-CA1 synapse .............................................................................................................. 64
3.5.1 Regulation of synaptic transmission and synaptic plasticity at pp-CA1 and SC-CA1
synapses by NMDA glutamate receptors .............................................................................. 64
3.5.2 Regulation of synaptic transmission at pp-CA1 synapses by group II metabotropic
glutamate receptors ............................................................................................................... 67
3.6 Learning-facilitated plasticity in pp-CA1 synapses ............................................................... 70
6
4. Discussion................................................................................................................................. 74
4.1 Summary. 74
4.2 Detailed discussion.................................................................................................................. 76
4.2.1 Challenges in obtaining pp-CA1 evoked potentials in vivo ............. 76
4.2.2 Comparative characteristics of evoked potentials at pp-CA1 and SC-CA1 synapses ...... 79
4.2.3 Ultra short term plasticity at pp-CA1 and Sc-CA1 synapses ........................................... 81
4.2.4 Long-term synaptic plasticity at the pp-CA1 synapse...................... 84
4.2.5 Regulation of synaptic plasticity at