Changes In Projection Neurons Research Articles

A Whole-Brain Cell-Type-Specific Sparse Neuron Labeling Method and Its Application in a Shank3 Autistic Mouse Model.

Single neurons, as the basic unit of the brain, consist of a cell body and processes, including dendrites and axons. Even neurons of the same type show various subtle process characteristics to fit into the diverse neural circuits. Different cell types of neurons form complicated circuits in the brain. Therefore, detailed neuronal morphology is required to understand normal neuronal function and pathological mechanisms, such as those that occur in autism. Here, we developed a strategy to sparsely label the same type of neurons throughout the whole brain and tested its application in an autistic animal model—Shank3 knockout (KO) mice. To achieve this, we designed an adeno-associated virus (AAV) that expresses Cre recombinase-dependent regular and membrane-targeted enhanced green fluorescent protein (EGFP) under a human synapsin 1 promoter and verified it in several Cre transgenic mice. We could sparsely label the projection neurons in multiple brain areas by retro-ocular injection of the virus into CaMKIIα-Cre mice. Then, we analyzed the morphology of the projection neurons in Shank3 KO mice with this method. We found differential dendritic complexity and dendritic spine changes in projection neurons in Shank3 KO mice crossed with CaMKIIα-Cre mice compared with littermate control mice in the striatum, cortex, and hippocampus. By combining this method with various Cre mouse lines crossed with mouse models of disease, we can screen the morphological traits of distinct types of neurons throughout the whole brain that will help us to understand the exact role of the specific cell types of neurons not only in autism spectrum disorder (ASD) mouse models but also in other psychiatric disorder mouse models.

Dopamine, acetylcholine and nitric oxide systems interact to induce corticostriatal synaptic plasticity.

Two distinct forms of synaptic plasticity have been described at corticostriatal synapses: long-term depression (LTD) and long-term potentiation (LTP). Both these enduring changes in the efficacy of excitatory neurotransmission in the striatum have a major impact on the physiological activity of the basal ganglia and are triggered by the stimulation of complex and independent cascades of intracellular second messenger systems. Along with the massive glutamatergic inputs originating from the cortex, striatal neurons receive a myriad of other synaptic contacts arising from different sources. In particular, while the nigrostriatal pathway provides this brain area with dopamine (DA), intrinsic circuits are the main source of acetylcholine (ACh) and nitric oxide (NO). The three neurotransmitter systems interact with each other to determine whether corticostriatal LTP or LTD is triggered in response to repetitive synaptic stimulation. Two distinct subtypes of striatal interneurons produce ACh and NO in the striatum. These interneurons are activated by the cortex during the induction phase of striatal plasticity, and stimulate, in turn, the intracellular changes in projection neurons required for LTD or LTP. Interneurons, therefore, exert a feedforward control of the excitability of striatal projection neurons by ensuring the coordinate expression of two alternative forms of synaptic plasticity at the same type of excitatory synapse. The integrative action exerted by striatal projection neurons on the converging information arising from the cortex, nigral DA neurons, and from ACh- and NO-producing interneurons dictates the final output of the striatum to the other structures of the basal ganglia.