Brainstem regions with neuronal activity patterns correlated with priming of locomotor stepping in the anesthetized rat.

Locomotor stimulation in the perifornical hypothalamus produces a transient facilitation of subsequent locomotion, a priming effect, such that stepping to a second train of stimulation occurs with a shorter latency of onset and increased amplitude. Neurons responsible for the initiation of this facilitated stepping presumably respond to locomotor stimulation with a similar priming effect, i.e. either a shorter latency or a larger change in activity rate. This study used anesthetized rats (urethane, 800mg/kg) to compare brainstem regions in terms of the relative rates of occurrence of single neurons that showed both specific responses to locomotor stimulation and also priming effects. Specific responses were characterized by a progressive increase in activity prior to the first step (a Type I pattern). In that they co-varied in time with the increased probability of stepping onset, Type I responses were more specific than Type II responses, which peaked early in the stimulation train several seconds before the onset of stepping. Regions with high proportions of neurons showing Type I responses and priming effects included the anterior dorsal tegmentum lateral to the central gray, the oral pontine reticular nucleus and the medial gigantocellular nucleus. Few Type I neurons showed a modulation of activity related to the step cycle. Type I primed neurons were uncommon in the cuneiform and the pedunculopontine regions, but neurons showing other patterns (decreases and antidromic responses) were relatively prevalent there. The ventral tegmental area was generally unresponsive. The results indicate that stepping elicited by perifornical stimulation in the anesthetized rat is mediated by circuits that differ at midbrain levels from the circuits implicated in other types of locomotion. Two regions, the anterior dorsal tegmentum and the oral pontine reticular nucleus, warrant further attention to determine their possible roles in the initiation of locomotion.

Hippocampal theta activity and facilitated locomotor stepping produced by GABA injections in the midbrain raphe region.

Inactivation of neurons in the midbrain raphe region produces increases in locomotor activity, and it appears that they function to suppress locomotion. Inactivation of neurons there also produces hippocampal slow wave (theta) activity and it appears that they also function to inhibit rhythmic activity in the hippocampus. We determined whether the degree of association between the two effects was consistent with the operation of a single mechanism. Stimulation electrodes were implanted into locomotor sites of the hypothalamus of 34 urethane-anesthetized rats. Hindlimb stepping was elicited by 5.12-s trains of perifornical electrical stimulation presented once per minute. Hippocampal theta activity was recorded across the CA1 layer of the dorsal hippocampus. GABA injections were used to locate raphe sites at which neuronal inactivation influenced stepping and hippocampal activity. A glass pipette (80-microm tip) was inserted into the midbrain, and injections of GABA (50-100 mg/0.1-0.2 microl) were made in 70 sites in the midbrain. Injections at 34 sites facilitated stimulation-elicited stepping, and at 17 sites, they also produced intertrial stepping. Facilitating injections, but not ineffective or suppressive injections, increased the mean peak frequency of hippocampal activity, and increased power in the 4-5 Hz band during the period that preceded the stimulation trains, but did not change the 5-6 Hz activity produced during the stimulation trains. Priming locomotor stimulation which also facilitated stepping produced generally similar increases in pre-stimulation peak frequency and 4-Hz power. The magnitudes of the increases in stepping and 4-Hz power were uncorrelated. The increase in 4-Hz power appeared earlier than the increase in stepping in 18 of 34 cases, and later in 11 cases; no increases in 4-Hz power were apparent in five cases. The results indicate that pre-locomotor 4-Hz hippocampal activity in the urethane-anesthetized rat is loosely coupled with facilitated locomotor initiation. Neurons in the midbrain raphe region appear to suppress both processes, but the low degree of association between the magnitudes and onset times of increases in stepping and hippocampal 4-Hz power indicate the operation of multiple mechanisms.