Refinement of neuronal networks in the rodent prefrontal cortex and hippocampus: critical impact of early and late social experiences [Elektronische Ressource] / von Reena Prity Murmu

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• Publié par: otto-von-guericke-universitat_magdeburg
• Publié le: 01 janvier 2008
• Nombre de lectures: 35
• Langue: English
• Poids de l'ouvrage: 8 Mo

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“Refinement of neuronal networks in the rodent prefrontal
cortex and hippocampus: Critical impact of early and late
social experiences”





D i s s e r t a t i o n



zur Erlangung des akademischen Grades



doctor rerum naturalium
(Dr. rer. nat.),



genehmigt durch


die Fakultät für Naturwissenschaften
der Otto-von-Guericke-Universität Magdeburg



von M.Sc. Reena Prity Murmu
geb. am. 22.03.1978 in Guwahati, Assam, India



Gutachter: Prof. Dr. Anna Katharina Braun
Prof. Dr. Hans-Joachim Bischof




Eingereicht am: 26.06.07
Verteidigung am: 06.12.07

1






Dedicated to my honorable

Mom (Mrs. Mariam Soren)

And

Dad (Mr. Dominic Murmu)

















2
ACKNOWLEDGEMENTS

I would like to express my thanks to Prof. Dr. Anna Katharina Braun for giving
me an opportunity to conduct my P.hD research work at her department. I would
also like to thank Dr. Jörg Bock, my supervisor for his guidance and supervision.
Many thanks to the technical staffs, Ute Kreher and Susann Becker for their
technical assistance.

I would like to acknowledge and thank our collaborators especially Prof. Micah
Leshem for designing this weaning project and supplying us the materials for our
morphological analysis. In addition, I would like to acknowledge and thank his
student Ms. Neta Ferdman for her significant contribution.

I express my sincere thanks to Ms. Kristin Michaelsen (TU Braunschweig) and
Andreas Abraham for helping me with the translations of my abstract.

I am greatly indepted to my wonderful life partner Mr. Oliver Elsner who I want
to particularly single out for his generous financial assistance and emotional
support without which I could not have accomplished my P.hD. I express my
special thanks to Mrs. Barbara and Mr. Eberhard Elsner for their support.

I would like to pay gratitude to my parents and thank them for everything that
they have done for me. I would also like to acknowledge and thank other members
of my family, Wilson, Victor, Celine and Trinity for their love and support. I have
had the privilege to work with my dear sister Ms. Meena Sriti Murmu at the same
department, and I thank her whole heartly for providing me every support that I
needed.

Reena Prity Murmu


3 ABSTRACT

The process of weaning programmes the physiological and neurobehavioural development of
various animal species and is thus a critical formative period for adult behaviour. The neural
substrates which may underlie these behavioural changes are largely unknown. This study for
the first time show that the timing as well as the amount of social contact with family members
significantly interferes with the refinement of prefrontal cortical and hippocampal synaptic
networks.

Studies have quite intensively investigated the critical importance of emotional experience (for
instance, time of weaning) at behavioural level. In addition, studies have provided compelling
evidence that during development environmental factors (such as social or isolated
environment) dynamically modify animal’s behaviour and brain development. Nevertheless,
the impact of these two different developmental time windows of emotional experience have
never been systematically studied and the neural mechanism remains unknown. In this study, I
tested our working hypothesis that during late childhood the neuronal networks in various
limbic areas such as the prefrontal cortex and hippocampus are reorganized in response to the
timing and the extent of social interaction with the mother and the siblings. This was done by
investigating the impact of time point of weaning (21 vs. 30), of social environments (social vs.
isolation) and in addition, by investigating the interactions between these two factors on the
neuronal morphology in the prefrontal cortex and hippocampus. The prefrontal cortex and the
hippocampus are part of the limbic system which are involved in emotional self-regulation and
the expression of emotional behaviours. Since, the time of weaning appears to be a major
emotional challenge during late childhood it can be assumed that this transition to
independence should involve major structural changes in limbic areas such as the prefrontal
cortex and hippocampus, which are involved in emotional behaviours.

The findings of this study demonstrate that emotional experience (i.e. the extent of social
experience with mother and the siblings) induces dendritic and synaptic reorganization, which
occurs in a highly temporal, regional and dendrite-specific manner. The development of spine
density was particularly sensitive to the amount of preweaning social experience, as the animals
that spent less time with their mother i.e. early weaned demonstrated elevated spine densities in
their dendrites of anterior cingulate cortex (ACd) and hippocampus. The dendritic length and
complexity of apical dendrites in the prefrontal area, anterior cingulate cortex (ACd) and
4orbitofrontal cortex (OFC) and in the CA3 area of hippocampus displayed only the interactions
between the factors time of weaning x postweaning social environment and not the effect of
time of weaning and social conditions alone. In the anterior cingulate cortex and in CA3 area,
the most socially deprived group (early weaning and isolated postweaning i.e. EWI) displayed
longer and more complex apical dendrites compared to other animals. In contrary, in
orbitofrontal cortex these animals displayed reduction in apical dendritic length and
complexity. In all these regions, the length and the complexity of basal dendrites remained
unaffected by either treatment. In dentate gyrus, the dendritic length and complexity of granular
neurons, mainly in the infra pyramidal layer of dentate gyrus displayed not only interactions
between time of weaning x postweaning social environment but also the influence of time of
weaning per se, and of social conditions alone. Similar to that in ACd and CA3, in dentate
gyrus the animals with fewest social experience or EWI demonstrated longer and more
complex infra and supra granular dendrites compared to other animals. Taken together, the
findings demonstrate that the timing as well as the amount of social contact with family
members significantly affects the refinement of prefrontal cortical and hippocampal synaptic
networks which as an integral part of the limbic system are essential for emotional and
cognitive behaviour.

In summary, the findings of this study may provide the neurobiological substrate for the
behavioural changes induced by different emotional experiences.











5TABLE OF CONTENTS
ACKNOWLEDGEMENTS............................................................................................. 3
ABSTRACT .................................................................................................................. 4
1.0 INTRODUCTION .................................................................................................... 8
1.1 Weaning: the process of separation and individuation of the young mammal ............................................. 9
1.2 Social environments: factors that dynamically shape adult behaviour and physiology............................. 12
1.3 The Limbic system: the emotional centre of the brain.................................................................................. 14
1.3.1 Limbic system part I: The prefrontal cortex (PFC) .............................................................................. 16
1.3.2 Anatomy and connections of the prefrontal cortex ............................................................................... 18
1.3.3 Neuropsychology and plasticity of the prefrontal cortex (PFC)........................................................... 21
1.3.3(A) Functions of medial prefrontal/anterior cingulate cortex (mPFC/ACd)................................... 21
1.3.3(B) Functions of orbitofrontal cortex (OFC) ......................................................................