Forward Dendritic Spikes - Advancing Artificial Intelligence Through Biological Process Applications - page 47

efficient and harmless to neurons the presence
of local dendritic spikes is recognized in more
cell types. Let's dig on it by reviewing the main
findings in one of the most paradigmatic cell type,
the pyramidal cell of rodents. For a rapid quali-
tative comprehension, always bear in mind that
the physiological (and computational) meaning
of the interaction between synaptic and intrinsic
currents depends on whether the later contribute
to the initiation or merely conduction of spikes,
and whether these reach the axon or not (i.e., cell
output).

which are performed in vitro , point to the axon
as the preferred site of action potential initiation.
There seems to be a considerable experimental
variability in pyramidal cells where it is claimed
that dendritic spiking precedes or follows axonal
firing (forward or backpropagation, respectively).
While in the later case dendrites are only notified
of cell output, in the former they become alterna-
tive zones for output decision (Stuart et al., 1997).
The challenge is served!
For a long time, the main approach to study
neuron activity was to evoke a response by stimu-
lating their afferent pathways. In highly dynamic
and non-linear systems as neuron dendrites, this
method has some disadvantages, as it puts the
emphasis on the strength and synchronization
of the input that may not reflect actual ongoing
behavior. The studies using synchronous activa-
tion of synaptic inputs showed that increases in
the intensity of the stimulus (i.e., the number of
activated synapses) produced a shift in the initial
locus of the outgoing spike from the axon initial
segment to a dendritic site, usually recorded in
the main dendrite (Turner et al., 1991). This led
some researchers to consider dendritic spike ini-
tiation as an abnormal response due to excessive
input synchronization, far beyond what might be
expected in spontaneous activity. However, the
strength of the input is neither the only nor the
main factor in determining the site of initiation.
Other researchers found subthreshold responses,
aborted spikes or fully propagated dendritic spikes
using identical excitation (Golding and Spruston,
1998). Additional factors, such as the frequency
of afferent input and local inhibition may also
shift the initial locus of the spike (Canals et al.,
2005).

The Data from Experiments

In pyramidal cells, active dendritic currents/poten-
tials have been shown either as slow components or
as local or fully propagated spikes (Andreasen and
Nedergaard, 1996; Golding and Spruston, 1998;
Herreras 1990; Masukawa and Prince, 1984; Wong
and Stewart, 1992). Most researchers consider
these active dendrites as weakly excitable based on
the dominant observation that most action poten-
tials initiate in the axonal trigger zone. This term,
however, is somewhat gratuitous as it intends to
open gap with fully excitable axonal membranes.
The issue is far from clear. We and other groups
have reported a sequential activation of synaptic,
slow subthreshold and fast spike-like inward cur-
rents in proximal apical dendrites propagating
toward the soma and axon (Herreras, 1990). We
later reported that specific damage directed to
the apical dendrites, or the local blockade of their
depolarizing intrinsic currents, was enough to stop
axonal firing upon large and synchronous synaptic
excitation (Canals et al., 2005; Herreras and Som-
jen, 1993). An important concept can be derived
from these observations. Thus, intrinsic currents
constitute the amplifying mechanism by which
the proximal main dendrite becomes a necessary
relay station for remote synaptic inputs to reach
the axon and cause cell output. While these are
population studies that report the average behavior
of a large number of cells, most single-cell studies,

Interpretations, Errors, and Other
Considerations

Experimentalists are bound to draw conclusions
from real data, but in the heat of the arguments
we often neglect the limitations of our techniques.