Biology Reference
In-Depth Information
Kindling and plasticity
As stated above, the term “kindling” refers to the experimental procedure of inducing
synchronous electrical afterdischarges and increases in susceptibility to additional
electrographic and behavioral seizures by repeated small electrical or chemical stimulation to
the brain [2, 35-38]. Kindling has been studied not only as a model for epilepsy, but also as a
form of long-term neural plasticity since it results in a permanent change in the nervous
system. It is likely that kindling protocols trigger a very large number of signaling pathways,
some of which are presumably still unknown. Some of these pathways appear similar to those
activated by LTP protocols, and thus investigators have hypothesized that the kindling
process involves an LTP-like process.
In his pioneering work that led to the “discovery” of kindling, Goddard [35] was actually
interested primarily in the effects of brain (amygdala) stimulation on learning. That kindling
involves learning-related mechanisms focused much of his attention on learning. Subsequent
studies on animals showed that as the
number of kindling trials increases so too do the animal's learning disabilities [2, 35-38].
The precise neurophysiological mechanisms for these learning and memory deficits seen in
kindled animals - or in epileptic patients - have not yet been determined. However, one
suggestion has been that alterations in the capacity of hippocampal neurons to sustain LTP
could play a role in this regard [47].
Mossy fiber sprouting and plasticity
Many investigators work with the dentate gyrus subfield of the hippocampus as a model
system for studies that involve plasticity and epilepsy since this region shows a great deal of
functional plasticity, such as mossy fiber sprouting after repeated seizure activity [7]. In
addition, mossy fiber sprouting can be examined using Timm staining [7]. The Timm method
stains neuronal elements containing heavy metals such as zinc, which is predominant in the
terminals of mossy fibers. Many of the types of changes that have been reported in the
hippocampus have been additionally documented in the neocortex. Interestingly, past studies
have reported that in vivo LTP trains (400 Hz; 1000 μA) induce mossy fiber sprouting when
non-epileptogenic stimulation was applied to the perforant pathway. The results also showed
that mossy fiber sprouting can be induced in the absence of neuronal degeneration, which
further suggests that sprouting is dependent on neuronal activity.
Does LTP play a role in mossy fiber sprouting?
Some studies do hint at the possibility there is an association (ie., but undefined) between
LTP and mossy fiber sprouting. However, there are several questions that remain to be
answered about this association. For example, do LTP protocols directly induce mossy fiber
sprouting? If so, is LTP-induced mossy fiber sprouting associated with neurodegeneration?
Finally, what forms of LTP lead to sprouting? The first evidence that LTP stimulation
protocols induce mossy fiber sprouting was produced by Adams et al. who showed that 400
