Plasticity Models for Aging and Neurodegeneration

Dr. Hayder Amin

Areas of investigation/research focus

The laboratory is interested in understanding the interplay between molecular and cellular processes and functional plasticity consequences in neurophysiological states, aging and neurodegenerative disorders.
We use multidisciplinary experimental and computational approaches to examine multiple forms of plasticity as changes in the electrical and chemical signals in large-scale networks at single-neuronal details.

The adult brain is a uniquely plastic organ capable of generating new neurons throughout life to modify its structure and function to continuously learn and adapt to changes in everyday experience and environmental demands. These activity-dependent plasticity changes can be ‘functional’, where neurons, adjust their electrophysiological properties. They can also be ‘molecular’, involving the regulation of particular gene expression patterns that are essential for the formation, maturation, and regulation of synaptic strength in those same neurons.

  • But how are functional and molecular processes of plasticity interrelated?
  • What is the functional role of newly-generated neurons in the adult brain?
  • What is the mechanism underlying the integration of these neurons into a resident network?
  • Importantly, how can the brain exploit these new neurons to stall the consequence demands of aging and neurodegeneration?

To address these questions, linking morphological, electrophysiological, and transcriptomic data at a single neuron in a large-scale network is essential but has lagged behind due to the lack of multimodal and multiscale techniques. Our laboratory aims to circumvent these challenges by using advanced molecular and cellular, electrophysiological, imaging and computation methodologies.

Projects:

Our research themes  involve projects in the following areas:

1. Neurogenic-plasticity models for aging and neurodegeneration: from genes to spikes

We aim to characterize the activity-dependent adjustments (from genes to spiking networks) of newly-generated neurons for the recruitment and functional integration into diseased or aged neuronal ensembles.

2. E/I balanced networks for empowering neuronal coding and synaptic stability

We study the long-term plasticity of excitatory and inhibitory (E/I) synaptic drive. We investigate how balanced E/I regime confers robust, and high-dimensional neural codes and computational performance.

3. Engineering the brain-on-a-chip (microfluidic channels integrated with CMOS-MEAs)

We design and implement systemic microfluidic platform on CMOS-MEAs to allow modeling different brain cell types for fundamental research, disease modeling, and drug development.

4. Bottom-up computational modeling

Our integrative approach aims to create a bottom-up comprehensive network modeling to simulate multi-level experimental plasticity readouts (molecular, cellular and networks).

5. Biofunctionalized platform for neural interfaces

We develop biofunctionalization methods to grow neuronal networks in well-defined configuration to investigate cell-to-cell and cell-extracellular matrix interactions. These methods also aim to improve the neuron-electrode interface to enhance the quality of the recorded neural signals.

Diseases related to these fields of research:

  • Alzheimer’s disease (AD)
  • Amyloid-beta toxicity (Aβ)
  • Parkinson’s disease (PD)
  • Amyotrophic lateral sclerosis (ALS)

Techniques: We build sophisticated approaches to index various neuroscience challenges from genes to networks by using:

  • In-vitro HiPSC-derived neuronal cultures and ex-vivo transgenic mouse brain slices
  • High-resolution CMOS-MEAs
  • Calcium imaging
  • Patch-clamp recordings
  • Genome-wide transcriptome profiling
  • Opto-and-chemogenetic
  • Molecular and cellular techniques
  • Micro-/nanotechnology
  • Computational modeling

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