Neuroplasticity in Information Processing within Interlamellar CA1 Hippocampus and in Schizophrenia


Student thesis: Doctoral Thesis

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Award date28 Aug 2019


The brain changes throughout life, based on experiences and environment. This ability of the brain to change (referred to as neuroplasticity) is involved in normal brain cognitive processes such as perception, learning, and memory. It is also involved in several brain diseases such as hearing loss, tinnitus, Alzheimer's, epilepsy, and schizophrenia. My thesis focuses on the involvement of neuroplasticity in normal cognition as well as brain diseases of tinnitus/schizophrenia.

This thesis covers the modification of excitatory neurotransmission in the hippocampus. The hippocampus is one brain region that has been studied extensively mostly due to its relatively simple architecture and its involvement in learning and memory. Researchers have revealed fundamental issues of neuroscience using brain lamellar (or transverse) orientation of hippocampus. The interlamellar network which is the longitudinal orientation of the hippocampus, however, has received very little attention until recently. It is predicted that the interlamellar network can also be involved in brain processes and plasticity. My research, therefore, shows how the interlamellar network of the hippocampus supports plasticity, namely, long-term potentiation (LTP) and long-term depression (LTD). Using techniques such as electrophysiology and 3D holography, it is demonstrated here that the interlamellar network has NMDA receptor-dependent LTP. However, there is no LTD under the frequently used LTD protocols. These results indicate that the longitudinal orientation has distinctive synaptic characteristics; hence it needs to be examined further for its significant contribution to brain function and diseases. I have shown in an experimental session how to obtain the longitudinal CA1 brain slice which is a somewhat novel approach.

Neuroplasticity is involved in diseases. One disease to which neuroplasticity is deeply linked is tinnitus (reviewed here). Chronic tinnitus is the perception of persistent ringing in one or both ears without the presence of external stimuli. The symptoms last the whole lifetime of sufferers after its inception. Chronic tinnitus is highly debilitating to sufferers due to its co-occurring factors such as insomnia, attention deficit, anxiety, and depression. Despite its negative impact on sufferers, there is limited therapeutic intervention to help relieve tinnitus. With tinnitus, there is a shift in neuronal excitation/inhibition (E/I) balance, which is modulated mainly by ion channels and receptors. The acting mechanism of most drugs is tightly associated with the balance of excitation and inhibition levels; I, therefore, reviewed the pharmacological interventions in tinnitus. The thesis brings out how altered function of ion channels and receptors in tinnitus relates to homeostatic E/I balance of the neurons and proposes the effective pharmacological intervention for tinnitus.

The last part of this thesis investigates a newly proposed concept in plasticity which could be the cellular mechanism for a neurological disease, schizophrenia. Short-term plasticity (STP), is another example of neuroplasticity that occurs in the brain. It is generally accepted that presynaptic activities underlie this form of plasticity. Recently, however, it has been shown by in vitro means that postsynaptic activity is involved in short-term plasticity. This postsynaptic activity is termed short-term postsynaptic plasticity (STPP). STPP can serve as the synaptic substrate for perception. Schizophrenia is one disease that presents with altered perception in the form of hallucinations. Therefore, STPP could play a crucial role in adding up to our understanding of schizophrenia pathophysiology in the line of altered perception. I believe that STPP could be a synaptic substrate for perception and be closely associated with schizophrenia. Thus, I intend to find the association of STPP with schizophrenia.

Neuroplasticity is the foundation for primary neuronal function in information processing in the brain and is also implicated in brain diseases. The study of neuronal plasticity is thus essential since it impacts on everyday normal and diseased life; it cannot be overlooked.

    Research areas

  • synaptic plasticity, hippocampus, schizophrenia, CA1, Long term potentiation, tinnitus