Ganong's Review of Medical Physiology, 23rd Edition

122
SECTION II
Physiology of Nerve & Muscle Cells

PRESYNAPTIC INHIBITION &

FACILITATION

Another type of inhibition occurring in the CNS is
presynap-
tic inhibition,
a process mediated by neurons whose termi-
nals are on excitatory endings, forming
axoaxonal synapses
(Figure 6–3). The neurons responsible for postsynaptic and
presynaptic inhibition are compared in Figure 6–9. Three
mechanisms of presynaptic inhibition have been described.
First, activation of the presynaptic receptors increases Cl

• con-
  ductance, and this has been shown to decrease the size of the
  action potentials reaching the excitatory ending (Figure 6–10).
  This in turn reduces Ca
  2+
  entry and consequently the amount
  of excitatory transmitter released. Voltage-gated K

• channels
  are also opened, and the resulting K


• 
  

  efflux also decreases the
  Ca
  2+
  influx. Finally, there is evidence for direct inhibition of
  transmitter release independent of Ca
  2+
  influx into the excita-
  tory ending.
  The first transmitter shown to produce presynaptic inhibi-
  tion was GABA. Acting via GABA
  A
  receptors, GABA
  increases Cl

  
  

• conductance. GABA
  B
  receptors are also present
  in the spinal cord and appear to mediate presynaptic inhibition
  via a G protein that produces an increase in K

• conductance.
  Baclofen, a GABA
  B
  agonist, is effective in the treatment of the
  spasticity of spinal cord injury and multiple sclerosis, particu-
  larly when administered intrathecally via an implanted pump.
  Other transmitters also mediate presynaptic inhibition by G
  protein-mediated effects on Ca
  2+
  channels and K


• 
  

  channels.
  Conversely,
  presynaptic facilitation
  is produced when the
  action potential is prolonged (Figure 6–10) and the Ca
  2+
  chan-
  nels are open for a longer period. The molecular events respon-
  sible for the production of presynaptic facilitation mediated by
  serotonin in the sea snail
  Aplysia
  have been worked out in
  detail. Serotonin released at an axoaxonal ending increases
  intraneuronal cAMP levels, and the resulting phosphorylation

  
  

of one group of K

+

channels closes the channels, slowing repo-

larization and prolonging the action potential.

ORGANIZATION OF

INHIBITORY SYSTEMS

Presynaptic and postsynaptic inhibition are usually produced

by stimulation of certain systems converging on a given

postsynaptic neuron (afferent inhibition). Neurons may also in-

hibit themselves in a negative feedback fashion (negative feed-

back inhibition). For instance, each spinal motor neuron

regularly gives off a recurrent collateral that synapses with an

inhibitory interneuron, which terminates on the cell body of the

spinal neuron and other spinal motor neurons (Figure 6–11).

This particular inhibitory neuron is sometimes called a Ren-

shaw cell after its discoverer. Impulses generated in the motor

neuron activate the inhibitory interneuron to secrete inhibitory

mediators, and this slows or stops the discharge of the motor

neuron. Similar inhibition via recurrent collaterals is seen in the

cerebral cortex and limbic system. Presynaptic inhibition due to

descending pathways that terminate on afferent pathways in the

dorsal horn may be involved in the gating of pain transmission.

Another type of inhibition is seen in the cerebellum. In this

part of the brain, stimulation of basket cells produces IPSPs in

the Purkinje cells. However, the basket cells and the Purkinje

FIGURE 6–9
Arrangement of neurons producing presynaptic
and postsynaptic inhibition.
The neuron producing presynaptic inhi-
bition is shown ending on an excitatory synaptic knob. Many of these
neurons actually end higher up along the axon of the excitatory cell.

Motor

neuron

Postsynaptic

Presynaptic inhibition

inhibition

FIGURE 6–10

Effects of presynaptic inhibition and facilitation

on the action potential and the Ca

2+

current in the presynaptic

neuron and the EPSP in the postsynaptic neuron.

In each case, the

solid lines are the controls and the dashed lines the records obtained

during inhibition or facilitation.

(Modified from Kandel ER, Schwartz JH,

Jessell TM [editors]:

Principles of Neural Science,

4th ed. McGraw-Hill, 2000.)

EPSP in

postsynaptic

Presynaptic neuron

action

potential

Ca^2 + current in

presynaptic neuron

Presynaptic inhibition

Presynaptic facilitation