lABORATORY OF Cortical Circuitry

 

 

About our Research

Anatomical Studies

Physiological Studies

Joshua Brumberg, Ph.D.
Professor,
Principal Investigator

Cortical Circuitry

The function of an electronic device such as a transistor radio can be explained based on its identifiable circuit elements; resistors, capacitors and transistors. Similarly, understanding the individual elements of a cortical circuit and how they interact brings us a step closer to understanding the function of the circuit as a whole and ultimately its behavior in response to environmental stimuli. While the analogy applies to the neocortex, deciphering the cortical microcircuit is much more difficult due to the diversity of components and the numbers of interconnections between the different elements. The focus of the Brumberg’s lab research is to characterize development and the neurons of the rodent barrel cortex with an emphasis on the interactions between the sensory and motor systems that govern the animals whisking behavior.

 

Techniques

 

 

Our goal is to define the circuit elements that comprise S1 and M1 and how they are influenced by environmental experience.Using the Golgi-Cox silver impregnation technique, we have characterized the normal morphological development and have defined the morphological classes of neurons in layer VI of barrel cortex. We have demonstrated that sensory deprivation (via whisker clipping) leads to changes in spine (the major site of input onto cortical neurons) morphology length and we are currently investigating how altering glutamatergic inputs (via transgenic mice and pharmacological approaches) can possibly provide a mechanism for the observed morphological changes.

 

Similarly we have shown that sensory deprivation impacts the extracellular matrix within the barrel cortex and the extent of myelination within the barrel cortex. Studies are ongoing to determine the functional significance of these anatomical changes. Using tract tracing methods we have characterized the reciprocal connections between the primary motor cortex (M1) and the primary somatosensory cortex (S1). This pathway is thought to be important for conveying information necessary to allow the motor system to update its motor plans in order to adapt to changes in the sensory periphery. Finally, using retrograde tracing methods we have focused on the anatomy of the neurons involved in the reciprocal connections between the cortical hemispheres (callosal neurons) and the thalamus and cortex (thalamocortical and corticothalamic neurons).

Electrophysiology

 

By understanding a neuron's intrinsic properties and the nature of the inputs it receives, it will be possible to construct wiring diagrams that inform our understanding of how cortical circuits function.We utilize both sharp intracellular and whole cell patch clamp recordings to characterize the intrinsic properties of neurons and study the nature of their inputs. In many instances, we use retrograde tracers in conjunction with our recording studies to correlate a neurons’ intrinsic properties with its axonal target.

 

We have developed a novel in vitro slice preparation that contains the whisker representations of both the primary motor cortex (M1) and S1 (barrel cortex) and maintains their synaptic connectivity. Recent whole cell patch clamp studies in the lab have focused on the morphology and physiology of identified callosal and corticothalamic neurons. It appears that callosal neurons in layers II/III and layer V have very homogeneous physiological properties but the laminar targets of their callosally projecting axons target different lamina and their synaptic inputs differ. Layer VI corticothalamic neurons appear to have intrinsic properties that differentiate themselves from their neighboring pyramidal neurons.

 

In collaboration with Daniel Simons’ laboratory at the University of Pittsburgh we have been studying the intrinsic and circuit properties of identified corticothalamic neurons in vitro. In collaboration with Christopher Moore at Brown University we have begun to study how changes in neural vasculature can impact neuronal functioning

 

Recently we have begun to use in vivo recording techniques to understand how animals process sensory stimuli. Through this integrated approach we are attempting to define the neuronal building blocks and their synaptic partners within mouse barrel cortex to understand the structure and functions of the cortical micro-circuit which is thought to underlie cortical computations and cognitive functions.