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. Key words: striatum; electrophysiology; S-R habit; chronic recording; dopamine; movementThe lateral striatum contains a population of neurons that discharge spontaneously at low rates and phasically in relation to sensorimotor activity of individual body parts. Their functional organization is in register with convergent, patchy somatotopic projections from primary somatosensory and motor cortices (

No abstract

No abstract

To investigate striatal mechanisms underlying the acute effects of stimulants on motor behavior, firing rates (FRs) of striatal neurons related specifically to vertical head movement were studied exclusively during vertical head movements. Precocaine FRs were recorded after intraperitoneal saline injection (time 1; T1), and rats performed conditioned vertical head movements (Ͼ10,000) similar to those induced by stimulants. After cocaine injection (0, 5, 10, or 20 mg/kg; T2), animals continued in the task. The proportion of long head movements was increased by low doses but decreased by the high dose, which induced stereotypic head movements. Comparing each neuron's FR during movements that were matched between T1 and T2 (e.g., regarding direction, distance), cocaine's effects depended on predrug FR and dose. Plots regressing T2FR on T1FR showed dose-dependent, "clockwise" rotations of regression lines in plots of all the neurons' average FRs and of individual neurons' FRs during different movements. All three doses elevated normally low FRs; the high dose also suppressed many higher FRs. Enhancement of a neuron's FR associated with weak and suppression of FR associated with strong corticostriatal inputs contradict several current theories of dopamine (DA) function. Induction of stereotypy by a single, high-dose injection suggests that this cocaine level exceeded that in other studies using cocaine self-administration, in which stereotypy develops only after several sessions. Suppressive effects observed only at the high dose and in numerous electrophysiological studies of DA agonist effects may be unrepresentative of uniform elevations in lateral striatal firing related to movement observed at lower cocaine levels.Effects of psychostimulants include increased rates of grooming, social activity, rearing, and locomotion at low doses; increased rates of locomotion and rearing at the expense of feeding, grooming, and social activity at moderate doses; whereas complex movements are replaced by short, repetitive, apparently purposeless movements, termed stereotypy, such as head bobbing at high doses (Lyon and Robbins, 1975). Dopamine (DA) transmission in the lateral striatum plays a key role in psychostimulant-induced stereotypy (Creese and Iversen, 1974;Kelly et al., 1975), more so than non-DA monoamines (Fog and Pakkenberg, 1971;Creese and Iversen, 1974). DA agonists in the lateral, but not medial, striatum cause stereotypy (Kelley and Delfs, 1994). DA antagonists or 6-hydroxydopamine lesions of striatal DA attenuate psychostimulant-induced stereotypy (Kelly et al., 1975).Glutamatergic projections from somatic sensorimotor cortices converge in dorsolateral striatum (DLS) (Kü nzle, 1975;McGeorge and Faull, 1989). Striatal medium spiny neurons (MSNs) fire in relation to sensorimotor activity of particular body parts (Crutcher and DeLong, 1984;Carelli and West, 1991) and project via pallidum and substantia nigra pars reticulata to thalamocortical premotor areas (Parent and Hazrati, 1995). The convergence onto M...

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.