뇌과학 연구 소개

김창업 (MD(DKM), PhD)

Biointelligence Lab

Brain Science (뇌과학)…? -뇌인지과학, 뇌신경과학, 뇌공학,…etc

뇌과학 관련 연구실을 실제로 찾으면…

• Neurobiology (animals, cells, tissues 대상) • Molecular biology • Electrophysiology • Behavioral study

• 대다수의 생물학, 기초의학 연구실. 주로 세포, 시냅스 수준에서의 분자기전 규명에 집중.

• Brain imaging (PET, MEG, fMRI, EEG, human 대상)

• Clinic-based(의대, 병원위주) • Psychology-based (심리학, 인지과학) • Engineering-based (공학, 물리학, 통계학 등 methodology)

• Theoretical (computational) neuroscience

• 국내는 아직 초기 단계

Experimental approach (data acquisition & analysis) &

Theoretical (computational) approach (modeling & simulation)

Functional MRI EEG(electroencephalography)

DTI (diffusion tensor imaging)

Brainbow

CLARITY

Electrophysiology (path clamp) Electrophysiology

(in vivo multi-electrode array)

PET (positron emission tomography)

How to get data from the brain?

Neural activity recording technologies

Two separate strategy & community

1. Macro to micro (human, medicine, psychology, imaging…)

2. Micro to macro (animal, neurobiology, electrophysiology…)

• Continuing innovation in imaging technologies (rather than electrophysiology)…

Microscale level (gene, molecule, cell, synapse)

Macroscale level (brain regions, brain networks) Mesoscale level (neuronal circuits, neuronal networks)

Microscale, mesoscale, and macroscale research

• Microscale의 연구(전통적으로 연구되어온 신경생물학)나 macroscale의 연구(90년대 이후 급격히 발전한 뇌연상 연구)에 비하여 mesoscale(개별 신경세포 해상도, 수십-수백개의 신경망)의 연구는 아직 미약함. Mesoscale에서 신경망 활동의 시공간적인 정보를 획득할 수 있는 기록기술의 부재 (MEA의 경우 공간정보의 제약이 심함).

미시적, 환원주의 중심의 연구경향에서 대량의 신경활성데이터의 가치에 대한 이해부족 및 분석역량 부족.

• 미시-거시적 지식 사이의 간극(gap) 발생

• Gene,moleculesynapseneural network behavior의 인과사슬에서 neural network 부분을 가능한 선형적으로 가정, 단순화함으로써 미시적 지식과 행동을 연결시키려 함 (실험신경과학자)

• 신경망의 spatiotemporal complexity를 이해하기 위하여 제한적인 데이터를 바탕으로 computational modelling & simulation을 수행 (계산신경과학자)

Mesoscale level에 대한 이해부족

How does the brain represent sensory information? -Revisits with two-photon imaging (masoscale level)

2011, Science

2010, Nature Neuroscience

2009, Neuron

Functional approach & Structural approach

DTI (diffusion tensor imaging)

3D electron microscopy

CLARITY Functional MRI Functional connectivity (fMRI)

Electrophysiology

Two-photon calcium imaging

새로운 연구동향

• 부분에서 전체로. • Bridging the gap! • Data driven neuroscience

BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative –also referred as BAM (Brain Activity Map) Project

On 2nd April (2013) Barack Obama announced the American Government would be backing the project by approving a $100m funding budget f or its first year of operation. Obama mentioned the project as a grand scientific challenge akin to the Human Genome Project. -Aiming to record every action potential from every neuron within a circuit.

1. Transformative Approaches for Cell-Type Classification in the Brain

1) provide cell census data in the whole brain, a brain region, or a significant functional circuit in the vertebrate nervous system 2) integrate molecular identity of cell types with connectivity, morphology, and location 3) apply statistical methods for creating a taxonomy of cell types based on molecular identity and connectivity 4) provide realistic estimates on the number/percentage of defined cell types in specific region(s) and/or circuit(s) 5) provide a basis to map cell types based on molecular identity and connectivity onto a reference brain atlas. “to develop a systematic inventory and census of cell types in the brain based on an integrated view of molecular identity (DNA sequence, single-cell transcriptomes, epigenomic information, and protein expression).” “This picture, in combination with information on anatomical connectivity and functional measures (e.g. physiology) will afford an unprecedented view of the vertebrate brain and provide a powerful foundation for future research.”

2. Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes in the Brain

• The tools sought through this FOA can include novel genetic or non-genetic methods for targeted delivery of genes, proteins, and chemicals to specific cells or tightly defined cell types.

• Functional activity라기보다는 anatomical한 circuit 정보.

Chung et al., 2013

3. New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System 4. Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System

• recording and manipulating neural activity, with cellular resolution, at multiple spatial and/or temporal scales, in any region and throughout the entire depth of the brain

• Technologies may engage diverse types of signaling beyond neuronal electrical activity for large-scale analysis, and may utilize any modality such as optical, electrical, magnetic, acoustic or genetic recording/manipulation

• A new generation of tools for optogenetics, pharmacogenetics, biochemical, electromagnetic and/or acoustic modulation needs to be developed

5. Integrated Approaches to Understanding Circuit Function in the Nervous System

• Applications should propose to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system.

• to provide resources for integrated development of experimental, analytic and theoretical capabilities for large-scale analysis of neural systems and circuits within the context, and during the simultaneous measurement of behavior.

• to elucidate a specific behavioral or neural system in terms of dynamic circuit activity.

• Experimental approaches should seek to employ model-based strategies where theories about causal mechanisms of circuit functions drive experimental approaches, and empirical data are interpreted in the context of quantitative theories of temporal dynamics and systems neuroscience.

6. Planning for Next Generation Human Brain Imaging

A. Paul Alivisatos et al., 2012.

Cognition Intelligence

actuator sensor

Environment

Cognitivism, computationalism (1950’ 反행동주의) Connectionism

(1980’)

계산주의, 인지주의 연결주의 체화된 인지

Brain & AI

Mathematics arises from our bodies and brains, our everyday experiences, and the concerns of human societies and cultures

Conceptual metaphors described in WMCF, in addition to the Basic Metaphor of Infinity, include: •Arithmetic is motion along a path, object collection/construction; •Change is motion; •Sets are containers, objects; •Continuity is gapless; •Mathematical systems have an "essence," namely their axiomatic algebraic structure; •Functions are sets of ordered pairs, curves in the Cartesian plane; •Geometric figures are objects in space; •Logical independence is geometric orthogonality; •Numbers are sets, object collections, physical segments, points on a line; •Recurrence is circular.

Embodied mind, Embodied cognition (1990’): 모든 추상적 개념, 언어 등이 몸을 통한 물리적 경험으로부터 발전. 고도의 추상화된 개념이라 할지라도 물리세계의 감각-운동 경험을 은유로 함으로써만 구성될 수 있음.

‘knowledge’에 대한 메타포

Giovanni Pezzulo et al., 2011

https://www.eucognition.org/

http://pages.isir.upmc.fr/EvoNeuro/moin.wsgi