Neuromodulation of motor systems

Among many reviews about CPG funciton, I like this one by Ole Kiehn and Paul S. Katz.
The introduction starts with a brief talk about dancing.

"...by changing cellular and synaptic properties, neuromodulators choreograph circuits from an ensemble of interacting neurons capable f dancing with a variety of partners."

2. The elements of neuromodulation in motor systems: alterations of cellular and synaptic properties
The CPGs - Localized neuronal networks in the central nervous system control the timing of the coordinated muscle activities, capable of producing rhythmic movement even when isolated from the sensory input (Delcomyn 1980).

The CPG function depends on synaptic interconnections and intrinsic membrane properties.
Neuromodulation changes both of them.

1) Rewiring circuits
We may often think of the nervous system as a hard-wired device whose connectivity is changed only during the developental period or as a result of learning.
NO, the strength of connections between neurons is not fixed, but can vary continusously under moment-to-moment neuromodulatory control.
The wiring diagram for a circuit is merely an outline of potential connections and does not uniquely determine the flow of information at all times.
- Modulation of chemical transmission
The effect of neuromodulation can be a functional disconnection of cells or a strengthening of the communication between cells.
Thus, the wiring diagram of synaptic connections is strongly dependent upon which neuromodulator is present.
In vertebrate locomotion, 5-HT and noradrenaline modulate glycinergic synapses to increase circuit flexibility.
- Modulation of electrical coupling

2) Changing neuronal personalities

- Modulation of resting conductances can determine neuronal participation in a network

- Modulation of conductances involved in phase transisions

- Modulation of conductances that determine spike rate

- Modulation of conductances underlying neuronal bistability

- Modulation of conductances underlying conditional bursting


3) Changes in cellular and synaptic properties produce secondary effects

The differential actions of neuromodulators on neurons in motor circuits underlie some forms of behavioral plasticity such as motor pattern selection.


3. Choreographing motor patterns: the effects of neuromodulators on the output of motor circuits

Neuromodulatory substances can initiate motor patterns by endowing neurons with the properties that are needed to form a functional CPG circuit.
Neuromodulatory sunstances can alter (or reorganize) motor patterns by changing those properties.

1) Neuromodulators can activate motor patterns
As a rule, the initiation of rhythmic movements requires non-rhythmic input from a source external to the CPG network itself.
-fast synaptic input (tadpole escape)
-neuromodulatory input (Tritonia swim, cats, rats, rabbits)

2) Neuromodulators can alter ongoing motor activity
- changing the speed/frequency
- muscle force
- phase relationship

3) Neuromodulators can reconfigure networks
-stomatogastric system
- At the moment, little is known about these types of network reorganizations in CPGs other than those in the stomatogastric system. Reconfiguration in the larger neuronal networks that control thythmic activity in vertebrates is difficult to evaluate because the CPG networks are poorly difined and it is impossible to be sure that one has recorded from all possible members of a functional circuit.

4) Neuromodulation can alter the ability of a CPG to drive its follower motor neurons

4. INtegrating neuromodulation into neuronal circuits

1) Properties of neuromodulatory neurons

2) Sources of neuromodulation
- Extrinsic vs Intrinsic

3) Convergence of modulation

5. Long-term alteration of motor patterns
Fast proprioceptive adjustment mechanisms are plastic and that they can adjust to long-term changes in the sensory signaling.

- in spinalized cats where locomotion on a treadmill is evoked by L-DOPA injection, cutting the lateral-gastrocnemius-soleus nerve results in long-term up-regulation of the load-compensating effects from group I afferents in the synergistic medial-gastrocnemius nerve, allowing the cat to slowly recover its normal stepping behavior (Whelan and Pearson 1997).

Neuromodulatory inputs may play a role in promoting long-term plasticity of CPG circuits. In spinalized cats, daily intraperitoneal or intrathecal injections of the alpha-2 adrenergic receptor agonist, clonidine, enhanced the recovery of locomotion when combined with training on a treadmill (Chau et al., 1998).