Slow self inhibition in neocortical interneurons
Alberto Bacci, John Huguenard, David Prince
We have used patch clamp
recordings from CCK-containing, LTS neurons of the neocortex of rat to demonstrate
that this class of inhibitory interneurons produce a
powerful use-dependent self-inhibition. In other words, when these LTS neurons
are activated to generate output signals (action potentials) they release
chemicals onto themselves (autocrines), which
suppress excitability of the neurons and cause them to produce fewer action
potentials.
This effect is caused by
endocannabinoids, cannabis-related chemicals that are generated within the
brain. Such autocrine actions that are
mediated by endocannabinoids represents a new form of
signaling. Previous studies had
demonstrated mainly retrograde effects on neuron to neuron communication
through their so-call synaptic connections.
We showed that the LTS
neurons, in particular, would show slow self inhibition (SSI) following periods
of activity. The LTS cells are in a
position to control the flow of sensory information to the major neurons of the
cerebral cortex, the pyramidal neurons. LTS cells send their output inhibitory
signals to the dendrites (the recipient zone for incoming excitatory synaptic
signals) of pyramidal neurons and thereby "control" the synaptic
messages received there. The
cannabinoid actions on LTS cells would alter their function and therefore
remove the control of messages received by dendrites. This action may explain part of the cognitive
effects of marijuana. The following
cartoon is designed to help describe these findings:
Cartoon showing how endogenous cannabinoids regulate cerebral cortical excitability. A. A type of inhibitory neuron in the cortex called an LTS cell (blue neuron) connects to the portion of the red excitatory pyramidal cell that receives messages (dendrites, d). The incoming signals on dendrites are transmitted to the cell body (triangle) and are relayed on to other nerve cells via the axon (a). Downward arrow shows the main direction of information flow. The LTS cell normally restricts flow of information so that only a portion of incoming signals reach the cell body and are sent out through the axon. B. During times of increased activity, LTS cells are exposed to their own endocannabinoids (smoke) and inhibit themselves, relaxing their inhibitory "grip" on pyramidal cells. This allows an unimpeded flow of messages through the pyramidal cells (wide downward arrow) -- i.e. there is less filtering of the input. Similar actions may explain some of the cognitive effects of marijuana.
For more information see:
Brain creates its
own marijuana-like chemicals, scientists find
NEUROBIOLOGY: Endocannabinoids Are Autoinhibiting
Nature
Highlights: Endocannabinoid function
Forbes:
Pot Plays With the Brain