Firing rate dependent effect of cocaine on single neurons of the rat lateral striatum.

Cocaine's effects on striatal neurons related to vertical head movement were studied during a task requiring vertical head movement. The proportion of long-distance head movements was increased by low doses but decreased by the high dose, which produced stereotypic head bobbing. At all doses, normally low firing rates related to movement were elevated to a greater degree than were normally high firing rates. At the high dose, normally high firing rates were strongly suppressed, a restriction which may contribute to the decreased behavioral diversity characteristic of stereotypy.

Loss of lever press-related firing of rat striatal forelimb neurons after repeated sessions in a lever pressing task.

Lateral striatal neurons that fire phasically in relation to active movement of the contralateral forelimb (determined via daily sensorimotor examination) were studied during acquisition of cued lever pressing. Rats were trained to lift the contralateral forepaw from the floor to press a lever in the presence of a tone. The tone was presented 70 times per day (session) for 18 consecutive days. All animals acquired the task, evidenced by gradual improvements across sessions and eventual asymptotic levels in tone discrimination, reaction time, and efficiency of the lever press. Forelimb neurons fired in relation to the lever press during early sessions of acquisition but not after repeated sessions on the task. This difference in firing could not be attributed to differences in forelimb movements during lever pressing or to sampling from different populations of neurons in early versus late sessions. In view of evidence that striatal damage impairs acquisition of motor skills, the change in firing suggests that the striatal activity present in early sessions may be necessary for the acquisition of, but not the automatic performance of, learned motor responses.

Stimulus-related and movement-related single-unit activity in rabbit cingulate cortex and limbic thalamus during performance of discriminative avoidance behavior.

Neuronal discharges related to acoustic conditional stimuli and locomotive behavioral responses of 152 anterior and medial dorsal (MD) thalamic and cingulate cortical single-units sorted from multi-unit activity were recorded as rabbits performed in a discriminative avoidance task. The goals were: (1) to document the single-unit constituents of multi-site, multi-unit activity recorded previously in response to the conditional stimuli used for avoidance training; and (2) to document neuronal activity related to the onset of the behavioral avoidance response. Ninety-five units showed discriminative discharges: significantly different firing rates 90-700 ms after a foot shock-predictive conditional stimulus (CS+) than to a safety-predictive conditional stimulus (CS-). In accord with the multi-unit data, a majority of these units discharged at higher rates after the CS+ than after the CS-. The discharge rates of 87 units were greater during the 2-s period preceding the onset of avoidance responses than during comparable trial periods after CS-presentations followed by no response. Fifty-six of the 87 avoidance-related units exhibited a progressive ramp-like firing increase 2 s before the avoidance response, with the maximal discharge rate occurring 200 ms before the response. These dynamic pre-avoidance discharges occurred first in limbic thalamus then in cingulate cortex, suggesting that cortical pre-motor processing may confer temporal specificity upon a more generalized command volley relayed from thalamus. Unlike the multi-unit data, 24 neurons exhibited inverse discrimination, i.e., significantly greater discharges in response to the CS-than to the CS+. Also 27 neurons showed significantly more firing in the 2-s period before the end of CS-trials in which no behavioral response occurred, than in the 2-s pre-avoidance period on CS+ trials with responses. This "inverse' CS-related and pre-avoidance activity occurred at low incidence (< 15%) in all areas except the MD nucleus, wherein it was exhibited by 45% of the recorded units. The inverse activity may reflect the operation of local inhibitory neurons which suppress the discharges of other neurons in response to the CS-. The prevalence of inverse activity in the MD nucleus suggested an involvement of this area in behavioral inhibition.

Activation of single neurons in the rat nucleus accumbens during self-stimulation of the ventral tegmental area.

Single neurons (n = 76) were recorded in the nucleus accumbens septi (NAS) of rats self-stimulating the ipsilateral medial forebrain bundle (MFB) at the level of the ventral tegmental area (VTA). Responses evoked by rewarding trains of stimulus pulses fell into five categories. The first category (40% of the sample) was characterized by a single discharge at invariant latency in response to individual pulses of the train, and hence was termed "tightly time locked" (TTL). Two TTL neurons were collision tested, and both showed collision, suggesting that self-stimulation of the VTA may involve antidromic, and thus direct, activation of a substantial number of NAS axons. The second category (26%) was characterized by discharges that varied in latency from pulse to pulse and hence was termed "loosely time locked" (LTL). Responses of the remainder of the sample showed no coupling to individual pulses but were categorized based on general firing patterns during the train: excited (7%), inhibited (4%), and no change (23%). Irrespective of category, immediately after the self-stimulation session, the likelihood of evoked discharge at monosynaptic latency by single pulse stimulation of the ipsilateral fimbria was reduced (relative to pre-session level), concurrent with elevations in mean firing rate and motor activity. NAS neurons thus exhibit vigorous activation, apparently both antidromically and orthodromically, in response to VTA self-stimulation. The responses of certain LTL and TTL neurons increased as a function of pulse number in the train, suggestive of integrative mechanisms important for brain stimulation reward. Conduction velocities of directly activated (TTL) axons (0.41-0.65 m/sec) were slower than those previously reported for first-stage, reward-relevant axons. Nonetheless, an implication of direct activation of NAS (and other MFB) axons is that rewarding stimulation triggers action potentials that could invade all axonal branches, including those between the stimulation site and the soma, and send synaptic signals to target neurons. Such signals from NAS neurons could contribute to the increased motor behavior accompanying MFB self-stimulation, and/or could interact with dopamine-mediated signals projected to the NAS from reward circuitry.