What roles do tonic inhibition and disinhibition play in the control of motor programs?

Abstract

Animals show periods of quiescence interspersed with periods of motor activity. In a number of invertebrate and vertebrate systems, quiescence is achieved by active suppression of motor behavior is due to tonic inhibition induced by sensory input or changes in internal state. Removal of this inhibition (disinhibition) has the converse effect tending to increase the level of motor activity. We show that tonic inhibition and disinhibition can have a variety of roles. It can simply switch off specific unwanted motor behaviors, or modulate the occurrence of a motor response, a type of 'threshold' controlling function, or be involved in the selection of a particular motor program by inhibiting 'competing' motor mechanisms that would otherwise interfere with the carrying out of a desired movement. A suggested general function for tonic inhibition is to prevent unnecessary non-goal directed motor activity that would be energetically expensive. The reason why basic motor programs might be a particular target for tonic inhibition is that many of them involve central pattern generator circuits that are often spontaneously active and need to be actively suppressed for energy saving. Based on this hypothesis, tonic inhibition represents the default state for energy saving and motor programs are switched-on when required by removal of this inhibition.

Keywords: behavioral switching; disinhibition; modulation; motor program selection; tonic inhibition.

Figure 1

Tonic inhibition of the crayfish escape system (adapted from Edwards et al., with permission from Elsevier). (A) Mechanosensory neurons (SN) directly excite the Lateral Giant (LG) interneuron via an electrotonic synaptic connection (resistor symbol). The SNs also excite mechanosensory interneurons (INS) that are also electrotonically coupled to the LG. (B) Synaptic inputs to the LG. Inhibitory synapses responsible for tonic inhibition are located distally from the LG cell body as are the excitatory synaptic inputs. Synaptic inputs responsible for recurrent inhibition are located proximally to the LG cell body close to the spike initiating zone (SIZ).

Figure 2

Modulation of the snail feeding system by tonic inhibition (adapted from Staras et al., , with permission from Elsevier). (A) The semi-intact preparation used for electrophysiological recording showing the location of feeding CPG interneurons in the buccal ganglia. A feeding stimulus, sucrose, is applied to the lips. (B) Firing patterns (top) and synaptic connections (bottom) of the three main types of interneurons that form the feeding central pattern generator. One cycle of feeding activity is shown with the origins of the synaptic inputs indicated by connecting bars. The N1M fires during the first protraction (P) phase, the N2 (with truncated spikes) the second rasp (R) phase and the N3t the third swallow (S) phase of the feeding cycle. (C) Model summarizing the modulatory effects of satiation and hunger on the tonic inhibition of the feeding pattern. In satiated animals the N3t fires continuously and the consequent inhibitory effects on the N1M prevent bursting in this cell. In hungry animals, even with no food present, there are occasional feeding bursts in the N1M due to the lower rate of firing of the N3t. In feeding animals the tonic N3t is weak and insufficient to prevent sustained bursting in the N1M and the N3t fires phasically to become part of the feeding rhythm. The thickness of the continuous lines connecting the N1M and N3t cells (left) indicates the strength of the inhibitory effects between the cells and the dashed lines the absence of phasic inhibitory effects. (D) An experiment in the semi-intact preparation showing that a food stimulus reduces the suppressive inhibitory control by the N3t cell and releases rhythmic fictive feeding activity. The change in the pattern of N3t firing is emphasized by the top trace where the number of N3t spikes is accumulated in 3s bins. (E) Expansion of the boxed area shown in (D) shows the first cycle of fictive feeding activity in the N1M after the sucrose-induced reduction in N3t firing rate. The arrow under the N3t trace indicates the point at which N3t starts to hyperpolarize and its tonic spike frequency begins to decrease. This decrease in N3t firing is followed by complete suppression of N3t firing when the N1M becomes active and synaptically inhibits the N3t. The subsequent phasic N1M-N3t reciprocal inhibition leads to the alternating patterns of N1M/N3t firing seen throughout the feeding pattern that follows. In (A) to (C) a stick indicates an excitatory synaptic connection between neurons and a ball indicates an inhibitory synaptic connection.

Figure 3

Summary of neural circuits underlying tonic inhibition of tadpole swimming and motor pattern selection by the vertebrate basal ganglia (adapted from Lambert et al., (A) and Grillner et al., (B), with permission from Springer and Elsevier, respectively). (A) Tension in the mucus secreted by the head cement gland during attachment of the tadpole to a substrate like the edge of a dish, activates cement gland mechanosensory neurons (SN). The sensory neurons directly excite rostral hind brain (RH) neurons and mid hind brain reticulospinal neurons (MHR). The RH neurons excite the MHRs and provide an indirect route for effects on spinal cord circuitry. The MHR neurons provide GABAergic inhibition of the spinal swim circuits. During the more-or-less continuous attachment of the tadpole during the first post-hatch day sustained tonic activity in the cement gland sensory neuron leads to corresponding tonic activity in the MHR followed by suppression of swim behavior. (B) Cortical and thalamic areas provide excitatory synaptic connections to the striatal input area of the basal ganglia that is involved in movement induction and selection. Striatal neurons activate brain stem command centers by inhibiting the firing of pallidal neurons. In the absence of striatal activity, pallidal neurons fire at high rates and provide tonic inhibition to brain stem command centers that are responsible for the activation of motor programs for saccadic eye movements, locomotion and posture. The striatum thus provides a disinhibitory mechanism for the generation of basic movements. Striatal and pallidal control pathways are functionally organized to allow the selective disinhibition of particular motor programs. This is indicated by the division of motor programs into boxed compartments with a corresponding segregation of the inhibitory connecting pathways. All the inhibitory connections in these circuits are GABAergic. A stick indicates an excitatory synaptic connection between neurons or nuclei, and a ball an inhibitory synaptic connection.