TBA
Midbrain dopamine neurons send dense projections to the striatal complex, comprising the striatum and nucleus accumbens (ventral striatum). This projection is crucially involved in a range of functions extending from motivation to reward processing, cognitive learning and motor control, functions that are mediated by different striatal complex subregions. Dopamine neurons show some regional heterogeneity in their patterns of activity corresponding to their projections, but heterogeneity in their connectivity is only now being revealed. In particular dopamine neurons use two small molecule cotransmitters, glutamate and GABA. Glutamate cotransmission is mainly observed in the nucleus accumbens, while GABA cotransmission is mainly observed in the dorsal striatum. Although these observations strongly suggest regional heterogeneity of dopamine neuron transmission among sub-regions of the striatal complex, it has not been systematically studied. To begin to examine the regional heterogeneity of dopamine neuron connections, we have used optogenetics for selective activation of dopamine neuron synapses in three functionally distinct regions of the striatal complex. This has revealed that dopamine neurons use not only glutamate and GABA as fast transmitters, but also dopamine itself as a fast transmitter. The relative strengths of these connections varies dramatically across striatal complex subregions. Detailed mapping of synaptic connections has further revealed the unique nature of the most medial-anterior part of the striatal complex, the medial shell of the nucleus accumbens, where glutamate-mediated dopamine neuron connections to cholinergic interneurons are strongest. This appears to confer particular sensitivity to amphetamine, and suggests that plasticity in dopamine neuron connections to cholinergic interneurons play a crucial role in triggering amphetamine-dependent plasticity and behavior, with relevance to disorders of the dopamine system, namely addiction and schizophrenia.
Connectomics is a study aiming the complete map of brain, however, it has not been well presented that how it can actually contribute to neurobiology. In this lecture, we will learn the practical side of connectomics from a few examples. The lecture will largely be divided into two parts. In the first part, I will present recent findings of connectomics on the neural computation in the mouse retina. It has been shown that wiring specificity of different types of neurons, that can be identified from high-resolution electron microscope (EM) images, elucidates the functions of neurons. Specifically, we will discuss how the wiring specificity, when combined together with known physiology of neurons, can explain the perception of motion in the mouse retina. In the second part, I will review the methods for connectomics. The accurate and fast analysis of the huge amount of EM image data is a challenging task and crucial for the success of connectomics. I’ll introduce the EyeWire, a gamified pipeline for the image analysis. It combines the artificial and human intelligence for accurate and fast reconstruction. The artificial intelligence provides over-segmented 3-dimensional pieces of neurons and human intelligences, volunteered from internet, play a game to put the over-segmented pieces together to reconstruct the entire neurons.
One overarching challenge of clinical magnetic resonance imaging (MRI) is to quantify tissue structure at the cellular scale of micrometers, based on an MRI acquisition with a millimeter resolution. Diffusion MRI (dMRI) provides the strongest sensitivity to the cellular structure. However, interpreting dMRI measurements has remained a highly ill-posed inverse problem. Here we propose a framework that resolves the above challenge for human white matter fibers, by unifying intra-voxel mesoscopic modeling with global fiber tractography. Our algorithm is based on a Simulated Annealing approach which simultaneously optimizes diffusion parameters and fiber locations. Each fiber carries its individual set of diffusion parameters which allows to link them by their structural relationships.
Animals are intrinsically computational. They acquire sensory information about their environments, transform this information into neural representations and memories, and calculate and execute decisions based on recent and past experiences. We study brain and behavior in the roundworm C. elegans and the Drosophila larva. Applying recent advances in electron and light microscopy, we are able to reconstruct, manipulate, and monitor the neural circuits for interesting navigational behaviors like the escape response, chemotaxis, and thermotaxis in these small animals. I will discuss how we use connectomics, functional imaging, and neurogenetics to link brain and behavior in these small animals with remarkably complex behaviors.
The logic of biological networks is difficult to elucidate without (1) comprehensive identification of network structure, (2) prediction and validation based on quantitative measurement and perturbation of network behavior, and (3) design and implementation of artificial networks of identified structure and observed dynamics.
Mammalian circadian clock system is such a complex and dynamic system consisting of complicatedly integrated regulatory loops and displaying the various dynamic behaviors including i) endogenous oscillation with about 24-hour period, ii) entrainment to the external environmental changes (temperature and light cycle), and iii) temperature compensation over the wide range of temperature.
I will discuss the current and past studies on a mammalian circadian clock as an example of molecule-to-cell-level systems biology, and also discuss the challenges and opportunities towards the organism-level systems biology. Especially, I will introduce the current update on the whole-brain and whole-body imaging with single-cell resolution as well as its biological applications.
Neurons form a complex network, which work as functional circuit to regulate behavior in the brain. Little is known about how these circuit functions to regulate behavior since it had been impossible to control the activity of specific type of neurons among them. Recently developed experimental techniques, optogenetics and pharmacogenetics (chemicogenetics) enable control the activity of targeted neurons in the brain. These new techniques allow us to study the function of these network and behavior using the whole animal. Especially, instinctive behaviors such as feeding behavior, drinking behavior, sexual behavior and sleep/wakefulness were exhibited only in the whole animal. To reveal the regulatory mechanism of these instinctive behaviors, these new techniques are essential. Hypothalamic neurons containing peptides (orexin and melanin concentrating hormone) play important role in the regulation of sleep/wakefulness. These peptide promoters are used to express optogenetical or pahrmacogenetical probe molecules such as channelrhodopsin and hM3Dq. The activity of these peptide-producing neurons was controlled in vivo. In this lecture, I will briefly explain basis of each techniques and will introduce some examples of application for sleep research.
