This document summarizes information presented about neurons, glial cells, and neural plasticity mechanisms. It describes the different types of neurons and glial cells, how they connect and function. It discusses various techniques for visualizing neurons. It also summarizes concepts of short and long-term synaptic plasticity mechanisms like LTP and LTD, and how the strength of connections between neurons changes based on their firing patterns over time through processes like Hebbian and homeostatic plasticity. The document encourages thinking about applying this neurobiology knowledge to develop potential therapeutic approaches.

1. Rita Barakat
Center for Aphasia and Related Disorders (CARD)
University of California Berkeley
Wednesday, November 18th 2015

2.  The material covered in this presentation is a
summary of approximately one year’s worth
of an undergraduate Molecular Neurobiology
curriculum.
 If you have specific questions regarding the
details referenced in certain slides, I will be
more than happy to provide more
information!

3.  There are hundreds of different types of neurons, and it is estimated that
each neuron can form 1000 or more unique connections with other neurons,
creating the complex neural networks that we are able to visualize today.
 The way these connections relay information is binary, in that the electrical/
electrochemical signal transmitted is either excitatory (typically causing a
depolarization of the post-synaptic cell), or inhibitory (typically causing a
hyperpolarization of the post-synaptic cell).
 Below are some of the more “general”
classifications of these neuron cell types
(organized by morphology/ function):
◦ Horizontal Cells (A)
◦ Bipolar Cells (B)
◦ Multipolar Cells ( C)
◦ Stellate (Golgi Type II) Cells (D)
◦ Pyramidal Cells (E)
◦ Purkinje Cells (F)
◦ …AND MANY MORE!!

4.  Many visualization techniques have been developed for imaging neurons at the
single-cell resolution; below is a brief summary of some of these methods:
◦ Nissl Stain (ideal for visualizing the soma and distinguishing between cortical layers
in situ)
◦ Golgi Stain (ideal for visualizing single neuron morphology, a Potassium Dichromate-
based staining technique that is still relatively mysterious in terms of its staining
selectivity)
◦ Immunohistochemistry (ideal for staining neurons that express a specific receptor/
protein, utilizes the endogenous mechanism of antibody-antigen binding)
◦ Retrograde/ Anterograde/ Viral Tracing (involves the injection of a tracer molecule,
either a fluorophore or a dye, that will travel in the retrograde or anterograde
direction and stain the neurons that are connected within a particular circuit. The
viral transfection-version of this technique involves infecting a circuit with a virus,
such as the Rabies virus, that will allow for more precise visualization of the cells
connected in series)
◦ Two-photon Microscopy (a high-resolution imaging technique which involves the
ejection of two photons of equal magnitude but opposite sign wavelengths, such as
+/- 45 nm, which allow for a very narrow range of the receptive field to be
visualized)
◦ “Brainbow” (utilizes selective expression of fluorescent proteins that distinguishes the
soma, as well as some limited visualization of the axon extensions, of individual
neurons)

6.  For every neuron, there are on average ten glial cells assisting with various
physiological processes (acquiring nutrients, initiating an immune response,
myelination, etc.)
 There are five major Glial Cell types (the sixth type, known as the Radial Glial
Cell, is present primarily during development). Below is a summary of these
five types, their morphology, location and function:
1. Astrocytes (CNS): The most abundant glial cell, they are named for their star-shape.
They have been to shown to assist in providing neurons with nutrients/ oxygen.
2. Oligodendrocytes (CNS): The “myelinating” glial cell of the central-nervous system,
these cells are able to detect/ “decide” which axons should be myelinated, and wrap
around the axon to form a “process” that then signals for myelination.
3. Schwann Cells (PNS): Perform a similar/ same function to the Oligodendrocytes, but
on nerve fibers in the periphery. Unlike oligodendrocytes, these cells do not form a
process on the axon fiber, and need additional cell assistance to influence
myelination.
4. Ependymal Cells (CNS): These glial cells line the choroid plexus membrane in the
ventricles and produce CSF.
5. Microglia (CNS): The smallest and least abundant glial cell, they function as the
immune cells of the nervous system (initiate the immune/ inflammation response).

7.  While the majority of connections between neurons are formed between
axons and dendrites, the Axon fiber itself is essential in initiating and
propagating the electrochemical signal (the Action Potential) that ultimately
conveys information to downstream, “higher” brain regions.
 In Molecular Neurobiology and Biophysics, we think of the axon as being
analogous to a wire that would transmit electrical information in the form of
electron flow. Based on the principles of Ohm’s Law (V = IR), we can then
assign qualitative and quantitative values to different features of the axon
(such as the diameter, length, and degree of myelination).

8.  Particular synapses can be strengthened or weakened depending on the
frequency of firing from a pre-synaptic cell onto a post-synaptic cell. A high
firing frequency is associated with Short-Term Facilitation (STF), a
phenomenon that can last up to a few hours. A low firing frequency is
associated with Short-Term Depression (STD), which can decrease the
strength of a monosynaptic connection for a brief period of time.
 The primary difference between “short” vs. “long” term changes in synaptic
strength is the recruiting of proteins for transcription, which only occurs in
the cases of extreme high or extreme low frequency firing periods that
induce Long-Term Potentiation (LTP) or Long-Term Depression (LTD).
 A significant increase in the synaptic Calcium Ion concentration has been
linked to LTP, whereas a moderate increase has been linked to LTD.

9. “The cells that fire together wire together”!
 “Hebb’s Postulate” provides a pre-synaptic explanation for neural plasticity,
which applies primarily to small (mono- or di-synaptic) connections, that
explains the associative phenomenon between neural firing (see above
quote)
 A new classification for a form of Hebbian plasticity that relies on a close
temporal relationship between the pre-synaptic and post-synaptic firing is
referred to as “Spike-Timing Dependent Plasticity” (STDP).

10.  On a larger scale, synapses can encode relative strengths that ultimately
translate into meaningful information in the “higher” cortical areas. This pre-
and post-synaptic phenomenon is referred to as Homeostatic Plasticity, and
essentially involves the encoding of a “homeostatic” baseline strength of a
particular synapse that allows it to be distinguishable relative to neighboring
connections.
◦ Pre-Synaptic “Scaling”: A pre-synaptic neuron can modify its firing
magnitude/ frequency in order to control the strength of its relationship to
the post-synaptic neuron.
◦ Post-Synaptic “Modification”: The post-synaptic neuron cannot control the
magnitude/ frequency of the signal it will receive from the pre-synaptic
neuron, however, it can still maintain a relative synaptic strength based on
the degree of transmitter receptors are expressed on the cell membrane.

12. In thinking about Neuron/ Glial cell morphology and function in
a broader context:
• “How can we take advantage of the physiological properties of a unique
Neuron or Glial cell type in a potential therapeutic approach?”
 e.g.) The potential role of the oligodendrocytes in remyelinating spared neurons
post-lesion, and how exactly to trigger this process based on what is known about
oligodendrocyte activity in vivo.
In thinking about Plasticity (Hebbian vs. Homeostatic) in a
broader context:
• “How can we stimulate synaptic strengthening (LTP) in order to influence
the activity of a particular circuit?”
• e.g.) Providing electrical/ magnetic stimulation to a tract that has been damaged in
order to revive and rebuild the synaptic strength of the overall circuit
Combining the powers of Molecular Neurobiology and
Cognitive Neuropsychology! 