Functional synaptic connectivity and plasticity in the mammalian striatum

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Brain function relies on neurons communicating at specialized junctions, synapses. During development, neurons need to form specific pathways to build the brain. After these set patterns of connectivity are established, the synapses between brain cells need to be able to change their connections and activity, in order for the brain (and animal) to acquire new abilities and memories, and use them effectively. This capacity, `synaptic plasticity', is believed to be the basis of all information storage and processing in the brain. Much has been learned of the mechanisms of synaptic plasticity, but most of our understanding comes from one brain region, the hippocampus, an area important for navigation and new memory formation. However, how synaptic plasticity works in other brain regions is relatively poorly described. The basal ganglia are brain regions that are critical for motor learning, skill acquisition, behavioral control, and emotional choices. The striatum is the gateway into the basal ganglia. Striatal neurons receive huge amounts of input fibers from all areas of the cortex and the thalamus, which carry sensory, motor, memory, and motivational information, and are modulated by dopamine, which predicts rewarding outcomes. It is the job of the striatum and to determine from all this information what actions to take in any scenario. This relies on experience, so synaptic plasticity in the striatum must occur throughout life, and is especially important during adolescence when the drive to learning new behaviours and risk-taking is high. Long-lasting synaptic plasticity changes such as increases (LTP) and decreases (LTD) in the strength of synapses are well characterized in (male) juvenile rodent hippocampus, but are less well understood in the striatum. This is in part because the striatum is more complex, and because few labs look at glutamate and dopamine inputs together; both of which need to be examined to understand their roles in striatal development and maturation. This project concerns part of my lab's efforts to understand striatal glutamate and dopamine synapse development and plasticity. We will do this in adolescent and adult mice male mice, and also in female mice, which may develop differently and have been largely unstudied. We use electrophysiology techniques to record synapse activity and LTP / LTD of glutamate inputs, and electrochemistry to measure dopamine release in brain slices. We use light to activate specific types of neurons, and drugs to examine the fundamental ways this brain region works. We will determine how sex differences may change the development and plasticity of the striatum which is lacking in the literature. This information is valuable to many areas of science outside our interests here; the striatum is involved in addiction, and many psychiatric, developmental, and degenerative conditions. Knowing how the striatum works will help guide many others who seek to understand how it fails.