Kimberle M. Jacobs,
Anatomy & Neurobiology
Virginia Commonwealth University
Richmond, VA 23298
Spontaneous GABAA inhibitory currents
recorded from a layer V pyramidal neurons.
inhibitory currents from layer V pyramidal neurons in normal (blue) and
epileptogenic (white) neocortex.
Evoked inhibitory currents
with epileptogenic-like activity (arrows).
Layer V neocortical pyramidal
neuron filled with biocytin during patch clamp recordings.
Containing billions of neurons and
trillions of synaptic connections, the cerebral cortex may well
be the defining feature of the mammalian brain. Responsible for
consciousness, perception, abstract thought, memory, planning, and
language, the neocortex is what makes us human. This is
also evident in the evolutionary expansion of brain volume devoted to
neocortex. One of the most elegant features of the neocortex is its
modular design, consisting of repetitive elements whose function depends
on input. These components are defined during development by
successive stages of neuron birth, migration, differentiation, and
synaptic connection. The intricate connections between elements are shaped
during development with environmental influences. The incredible facility of the neocortex
for adaptation based on experience, learning, and maldevelopment has
become far more evident in the last twenty years.
One current challenge is to
identify which neuronal processes are plastic at each developmental stage
and how these processes are affected by common clinical maladies.
Brain damage during development can result from a variety of insults, such
as maternal infections, direct trauma, vascular infarction, genetic
abnormalities, and exposure to toxins, including alcohol and drugs.
These developmental perturbations will produce varying effects, depending
on timing, severity, and location. Disruption in the balance between
excitation and inhibition, producing seizures is a common result from any
of these insults, often accompanying other symptoms such as dyslexia,
mental retardation, and schizophrenia. Local changes in excitation
and inhibitory balance allow for desired forms of plasticity, such as
those required during learning. One goal is to understand the
modulators that permit the shift between local fluctuations and more
globally synchronized and detrimental imbalances of excitation and
the overall complexity of connections, individual cell types and circuits responsible for particular neuronal behaviors can be
principal interest is in identifying the cellular components and
mechanisms that allow for and produce specific forms of cortical plasticity.