How single cortical neurons compute information?

The pyramidal neuron is the basic building block of the brain. Unlike the chip of the computer which is a simple computing element, the neuron is a complex computing machine. It is complex both anatomically and functionally.
We seek to understand how different neurons in different cortical brain regions such as sensory, motor and olfactory integrate their incoming inputs.
For this purpose, we study dendrites, which are the main structures of the neurons that are the main recipients of synaptic information. Dendrites can be regarded as the computation powerhouse of the cortex and thus are crucial for understanding the input-output function, and ultimately encoding and decoding of cortical information.
We use brain slices of different cortical regions along with advanced microscopy, electrophysiology, uncaging of neurotransmitters, light activated manipulations and computer modeling to get insight into these complex, intricate and marvelous brain structures called dendrites. We believe that understanding how dendrites work is essential for our mechanistic understanding of how the brain works.


Plasticity mechanisms in principle cortical neurons.

One of the most basic characteristics of the brain is its ability to ever change throughout life from birth to death. In the lab, we are interested to decipher the cellular and molecular mechanisms responsible for long term plasticity changes in cortical neurons, changes that underlie the capacity of the brain to change and adapt to new experiences and challenges.
We study how synapses of different cell types and cortical regions change in response to previous experiences. We study a diverse brain regions and cell types as our main hypothesis is that different brain regions solve different learning and memory problems thus mechanisms may differ markedly between brain regions and cell types.
We use brain slices to record from soma and dendrites combined with advanced light activated and imaging methods along with computer simulations.


Mechanisms underlying motor representation and learning in the cortex.

A major effort in the lab is to decipher how information is represented in the brain and what are the changes that occur in the brain that are responsible for learning and memory of new experiences. Presently, we are concentrating on the motor system since it is an extremely important and conserved system throughout evolution of mammals.
We study fundamental questions regarding how we generate movement and learn new motor skills. We take two unique approaches to investigate neural computation mechanisms that underlie motor representation: 1. We study single-cell dendritic computations of pyramidal neurons (PNs) in M1 in behaving mice. We record from the input sites-the dendrites and from the somas-the output sites. Thus, we are able to address the question of what algorithms are used by neurons to transform their inputs to outputs to learn and code information. We believe this description level (single-cell input-output description) is critical for understanding the mechanisms of how motor information is computed and stored in the cortical network. 2. We study cell type dependent learning and computations in motor cortex in vivo and cell type related circuitry found in the motor cortex. The logic behind our approach is that the different cell types create specific parallel circuitries, each possibly differentially involved in different aspects of movement. Importantly, the different cell types provide an effective handle to manipulate the circuitry.
To get insight into these questions, we use new emerging techniques, including in-vivo two photon imaging in behaving rodents, Neuropixels electrophysiology, various dexterous and nondexterous motor tasks, viral and genetic methods including optogenetic and chemogenetic perturbation of targeted cells. In addition the lab has developed a unique platform to study single neurons and their dendrites in vivo with an unprecedented resolution in awake-behaving mice.


Cortical mechanisms in Parkinson’s disease

Understanding the mechanisms underlying cortical motor control may assist in understanding the mechanisms of various brain diseases such as Parkinson’s disease.
We are focusing on basal ganglia-cortical loops, which play a pivotal role in action initiation in normal brains and are central in the pathogenesis of Parkinson’s disease. A major target of our study are the M1 pyramidal tract neurons which receive the disrupted basal ganglia products via the motor thalamus ultimately resulting in attenuated excitatory drive to tuft dendrites of M1 PT neurons.
Toward this end, will use behavioral motor paradigms in mice models of Parkinson’s disease, combined with two-photon imaging of network and dendritic activity in-vivo as well as opto- and chemo-genetic manipulations of neuronal activity.