AMPA-type glutamate receptors and behavioural neuroplasticity : Bidirectional role of GluA1 subunits
Year: 2012
Type: dissertation
Abstract: Neuroplasticity is defined as an ability of the nervous system to change when it responds to modified environmental or internal conditions. Functional neuroplasticity enables a change in behaviour and ultimately provides a major mechanism for enhanced survival in a given environment. There are two main types of plasticity, positive and negative plasticity. Positive plasticity describes abilities and brain processes that benefit an animal. Negative plasticity is related to processes that tend to be harmful. In this study, positive neuroplasticity was investigated in relation to aggressive behaviour and processing of novel signals; processes that are both required for successful survival in a changing habitat. Negative plasticity was studied in several stages of addiction, a psychiatric disease in which normal plasticity is interfered by drugs of abuse eventually leading to compulsive drug use. The neurotransmitter glutamate has a well-established role in chemical signalling between neurons, and an emerging role as a major component regulating neuroplasticity. Glutamate receptors of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type are tetramers composed of subunits GluA1-4 and they mediate a majority of the fast synaptic neurotransmission, that is also implicated in neuroplastic processes. Here, the AMPA receptor subunit GluA1-deficient mouse line (GluA1-KO mouse line) was studied using behavioural and neurochemical approaches. GluA1-KO mouse line provides an alternative approach to study the importance of AMPA receptors in neuroplasticity, as there are no subunit-selective pharmacological ligands available. GluA1-KO mice displayed less propensity to change their agonistic behaviour when exposed to an altered social environment in comparison with wild-type (WT) control mice, increased responsiveness towards spatial novelty followed by deficient habituation, decreased capability to develop tolerance to benzodiazepine flurazepam, and defective morphine-induced state-dependency. Taken together, these results propose a bidirectional role for GluA1 subunit in positive and negative neuroplastic processes. In summary, these results strengthen the role of GluA1 subunit in neuroplasticity, and may assist future drug development in disorders in which neuroplasticity plays a role.
Source: Työväentutkimus Vuosikirja
Author: Teemu Aitta‐aho
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funder: Helsingin Yliopisto
OpenAlex ID: W1572557652