Download Larry M. Jordan, Urszula Sławińska

Chapter 17
The Brain and Spinal Cord Networks
Controlling Locomotion
Larry M. Jordan, Urszula Sławińska
Copyright © 2014 Elsevier Inc. All rights reserved.
1
FIGURE 17.1 The main contributors to the network in the brain for control of locomotion are superimposed on a sagittal
view of the human brain. The white arrows represent excitatory projections, while shaded arrows represent inhibitory
connections. The motor cortex can select a locomotor task by activating the basal ganglia (BG), where the striatum
provided inhibition to the BG output neurons of the globus pallidus. The globus pallidus and homologous basal ganglia
output neurons tonically inhibit the major components of the MLR, the cuneiform nucleus (CN) and the
pedunculopontine nucleus (PPN), so that BG activation leads to disinhibition of the MLR nuclei, resulting in the initiation
of locomotion through a relay in reticulospinal (RS) neurons. The BG output is monitored and fed back to the cortex
via the thalamus (Th). Another route for activation of the midbrain locomotor neurons is by excitation of the widespread
neuronal systems included in the diencephalic locomotor region (DLR), which can elicit locomotion either via activating
CN and/or PPN or by projections to the RS locomotor areas. The various DLR and MLR areas can be recruited to
produce locomotion due to activation from the cortex, limbic structures, and other parts of the brain in a variety of
conditions (e.g. arousal, exploration, and escape) where locomotion is an appropriate output. Multiple RS neuron
groups are able to activate the spinal CPG for locomotion.
Copyright © 2014 Elsevier Inc. All rights reserved.
2
FIGURE 17.2 Diagram showing the main components of the reticulospinal (RS) projections to the spinal cord to activate
the locomotor CPG. The RS systems that are effective for eliciting locomotion are distinguishable based upon their
transmitter content. Pathways containing excitatory amino acids (EAA) such as glutamate project from magnocellular
and gigantocellular parts of the RS system to the spinal cord. Other RS pathways arise in the 5-hydroxytryptamine (5HT) and noradrenergic (NA) regions of the medulla. The RS systems are known to be activated from the lateral
hypothalamus (LH), which includes an orexinergic (Ox) pathway, and from the components of the MLR, including the
cuneiform nucleus (CN) and the pedunculopontine nucleus (PPN). CN and PPN provide glutamatergic (excitatory
amino acid, or EAA) input to RS neurons, and PPN also produces RS activation due to a cholinergic (acetylcholine, or
ACh) projection. There is a newly described orexinergic input to neurons of the CN for initiation of locomotion. Another
putative component of the MLR is the A7 noradrenergic group of neurons found at the junction of the midbrain and the
pons, in a site where electrical stimulation elicits locomotion. These cells project directly to the spinal cord. A
dopaminergic (DA) pathway, thought to arise from the All group of dopamine-containing neurons of the hypothalamus,
may also be an important descending pathway for the initiation of locomotion in some species.
Copyright © 2014 Elsevier Inc. All rights reserved.
3
FIGURE 17.3 Models of the CPG. (A) The half-center model of Graham-Brown, as modified by Lundberg to explain the findings in LDOPA-treated spinal cats. Stimulation of ipsilateral flexor-reflex afferents (iFRAs) produced late-long lasting excitation of flexor
motoneurons, while stimulation of contralateral flexor reflex afferents (co-FRAs) produced similar excitation of extensor
motoneurons. The L-DOPA treatment produced locomotion in the spinal cat preparation, and the half-center model was proposed as
a plausible organization to explain these findings. (B) A computational model of spinal locomotor circuitry with a two-level CPG.31
Rhythm generator (RG) and pattern formation (PF) networks represent the two levels of the CPG. The excitatory RGE-E (rhythm
generator—extensor) and RGE-F (rhythm generator—flexor) populations reciprocally inhibit each other via the inhibitory RG
populations RGI. The PF excitatory populations (PFE) reciprocally inhibit each other through the PF inhibitory populations (PFI). The
RGE-E and RGE-F populations have recurrent excitatory connections. Locomotion is initiated by a tonic excitatory drive (from MLR
and/or MRF) to both the RG and PF populations. The locomotor rhythm and the durations of the flexor and extensor phases are
determined by the RG network that controls the activity of the PF network by direct excitation of PFE neurons (and inhibition to PFE
neurons mediated by the RGI populations—not shown). PFE population activity produces a phase-specific activation of the
corresponding group of synergist motoneuron (Mn-E and Mn-F) pools. Phase-dependent inhibition of motoneurons is produced by
the MnI-E and MnI-F populations whose activity is regulated by excitation from the PF network and inhibition from MnI neurons.
IaINs are included in the MnI population, and inhibition from Renshaw cells (not shown) as well as mutual inhibitory connections
between the MnI populations can also control MnI rhythmicity.
Copyright © 2014 Elsevier Inc. All rights reserved.
4
FIGURE 17.4 Diagram representing the progenitor domains (p0–p3) that give rise to ventral spinal interneuron groups
(V0–V3). The transcription factors that characterize the progenitor domains and the postmitotic interneuron subgroups
are illustrated. Where possible the transmitter phenotypes of the interneuron subgroups are given, along with their
known sites of termination. Motoneuron progenitors and their associated transcription factors are also illustrated.
Interneurons that express Hb9 (similar to motoneurons) are also illustrated, although the cardinal progenitor group that
produces them is not known. V0d: dorsal V0 interneurons; V0v: ventral V0 interneurons; V0c: cholinergic V0
interneurons; RCs: Renshaw cells; IaIN: Ia inhibitory interneurons; V2a: excitatory V2 interneurons; V2b: inhibitory V2
interneurons; MN: motoneurons; V3s: V3 interneurons producing synchrony; V3r: V3 interneurons with connections
expected of rhythm-generating layer neurons.
Copyright © 2014 Elsevier Inc. All rights reserved.
5