Description of differential plasticity properties in the rat striatum and its implications for L-DOPA-induced dyskinesia

Abstract

The striatum is the main input nucleus of the basal ganglia. Striatal subregions, which play different roles in motor functions, receive inputs from different cortical regions. Regulation of synaptic plasticity at the level of corticostriatal synapses is believed to underlie habit formation and motor learning. Alteration of plasticity at the level of corticostriatal synapses has been associated with dopamine depletion and is thought to underlie motor symptoms of Parkinson’s disease and Levodopa-induced dyskinesia (LID). Our aim in this study was to develop methods to characterize plasticity properties in striatal subregions in vivo through microstimulation and simultaneous large-scale electrophysiological recordings in a rat model of LID. For this, we built electrode implants with a sophisticated design. We stimulated the cortical afferents of the dorsomedial striatum (DMS), dorsolateral striatum (DLS), and ventral striatum (VS) to evaluate neuroplastic changes in each subdivision upon high frequency stimulation (HFS) and low frequency stimulation (LFS), ON and OFF Levodopa (L-DOPA). We recorded wideband neuronal activity in the studied cortical and striatal regions and measured changes in the amplitude of the evoked potentials (EPs) in the local field potential (LFP) in response to stimulations. We obtained differential changes in the amplitudes of EPs in LFP among different striatal subregions. In the dorsolateral striatum, HFS and LFS protocols did not induce noticeable changes in the amplitude of evoked potentials. In comparison, in the DMS, HFS and LFS protocols induced an increase and a decrease in the amplitudes of evoked potentials respectively. Such differential changes in the amplitude of evoked potentials might be an indicator to differential plasticity in the striatum.

Popular Abstract

Striatal plasticity: Secret key to end suffering of Parkinson’s disease Patients?


Our brain is fascinating. With it we think and dream. It controls our heartbeat, breathing, vision, hearing, and movements. Our brain is made up of different parts which contain cells called neurons that communicate, through nerve impulses, among each other in an astonishing way to control our body. People think that circuits in our brains are hardwired as computers, but they are not! Our brains are not static organs, they are rather malleable. They can rearrange the networks between neurons or even undo them to adapt to new experiences. It is largely through this mechanism that is called neuroplasticity we develop memory for scents, faces, or learn how to ride a bike, by strengthening certain connections and weakening others.

However, neural networks become altered sometimes which causes diseases such as Parkinson’s disease. Patients with Parkinson’s disease suffer from tremor, slow movement, stiffness, and loss of balance which makes it hard for them to do everyday things such as changing clothes and drinking. Sadly, there is no cure for this disease and treatments with drugs like Levodopa help to reduce these symptoms and improve life quality of patients but after long time of treatment the patients suffer from complications and develop other movement disorders called dyskinesia. Scientists believe that symptoms of Parkinson disease and dyskinesia are caused by abnormality in the communication of neurons in a brain structure called striatum.

In our project we were interested in understanding how neurons in the striatum modulate their communication and whether there are differences in their way of modulation among different subregions of the striatum because it has been suggested that these subregions play different roles in motor learning and development of motor symptoms of Parkinson’s disease. We developed methods to better understand how these neurons modulate the communication in normal state and in disease. We carried out the experiments in rat models of Parkinson’s disease. We induced neurons in a certain region of the brain of rats to send nerve impulses to neurons found in the different regions of the striatum and observed how cells communicate in the normal and diseased state. We compared the results obtained and found differences among the different regions, but these differences did not allow us to be certain that neurons in different regions of the striatum modulate their communication differently. Despite the results, we could develop new methods to study plasticity in alive freely moving rats unlike most of the experiments, carried out previously, that were done in brain tissues taken from sacrificed animals. We also improved the previously used tools and methods which will help our group and other groups to carry out experiments in the future in better conditions and get more accurate and credible results.

We hope that our project was one step forwards to better understanding of neuroplasticity in the striatum which might help in finding novel strategies needed to develop a better therapy for Parkinson’s disease making patients’ lives easier without developing any complications.

• author: Biado, Mahmoud
• supervisor: Per Petersson
• organization: Degree Projects in Biology
• course: BIOM02 20221
• year: 2023
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 9114038
• date added to LUP: 2023-05-05 13:32:43
• date last changed: 2023-05-05 13:32:43