A telerecording analysis of reaching disruptions in rats after stimulation or lesion

In the so-called "handedness" experiments rats learn to retrieve food pellets from a narrow tubular feeder preferentially with the left or right forepaw. Frame-by-frame analysis of videotape recordings showed that the stereotype movement consists of a fast forepaw extension (54 msec), followed by isolated finger flexion (46 msec) overlapping later with slow forelimb retraction (180 to 400 msec). Reach-triggered single pulse stimulation of contralateral caudate nucleus or ipsilateral dentate nucleus interfered with finger flexion and disorganized the time course of the movement. Electrolytic lesion of the ipsilateral dentate nucleus caused marked slowing of the extension (80 msec) and finger flexion (140 msec) phases of the movement. Videoanalysis confirms the ballistic character of the initial phase of the reaching movement.     

Effect of dentate cooling on lateralized reaching behavior in rats

The role of dentate nucleus in pre-programmed lateralized movements was studied in rats trained to reach for food pellets into a narrow tubular feeder. Local cooling of the dentate nucleus ipsilateral to the preferred forelimb (cryoprobe tip temperature 5°C) caused severe impairment of the movement, but the deficit was considerably compensated after 5 to 10 min of continued cooling. Cooling to higher probe temperatures (10°C) and/or repeated coolings elicited gradually attenuating movement disruptions. The results confirm participation of the cerebellar hemispheres in pre-programmed voluntary movement, but indicate at the same time that elimination of this link can be easily compensated.     

Intracranial colchicine impairs lateralized reaching in rats

Unilateral intracranial administration of colchicine was used to interfere with the lateralized reaching-for-food habit (‘handedness’) in rats. Epidural application of colchicine (500 μg/10 μl) over the motor cortex contralateral to the preferred forepaw caused a partial blockade of reaching, culminating after 3–4 days and recovering after 7–10 days. The same amount of colchicine applied on the occipital cortex or on the motor cortex ipsilateral to the preferred forepaw did not affect reaching. Injection of colchicine (2 μg/2 μl) into the contralateral substantia nigra caused an almost complete impairment of reaching on Days 2–5. Recovery started on Day 6 but the initial performance level was not attained even 2 weeks after the injection. Blockade of reaching induced by the injection of colchicine (5 μg/5 μl) into the contralateral caudate nucleus had a similar intensity and time course but recovery was faster. Histological examination revealed signs of partial tissue damage up to 500 μm from the site of injection.The results confirm the feasibility of using colchicine for reversible blockade of discrete brain areas but indicate at the same time that some of the effects of chochicine are irreversible.     

Characteristics of the Performance of a Formed Motor Skill by Rats with Different Motor Preferences

Wistar rats with different motor preferences were used to study performance of a food-procuring skill – extracting food from a narrow horizontal feeder tube. These experiments showed that when the preferred limb was used, left-handed rats performed the task more quickly (including both preliminary movements and the final successful movements) than right-handed rats. Comparison of movement performance times with the preferred and non-preferred limbs showed that the task was performed more quickly using the left paw in both left- and right-handed rats, i.e., independently of whether this was the preferred paw or not. At the final stage of task performance (grasping and extracting the food), the preferred paw was more successful than the non-preferred paw in both right- and left-handed animals. It is suggested that the organization of the overall strategy for performing this complex behavioral task in rats is determined by the functional heterogeneity of the right and left hemispheres of the brain, which is not linked with limb preference. The selected preference is based on the specific motor and precision characteristics of the preferred paw, while the contralateral hemisphere – the left in right-handed animals and the right in left-handed animals – has a special role in mediating these abilities.     

The Formation of Lateralized Motor Habits in Rats

Wistar rats were trained to obtain food from a narrow tube feeder using the forepaw in conditions of free choice of which limb to use. It was found that the presence or absence of limb preference, identified in short preliminary tests, often did not coincide with the nature and degree of lateralization formed during the process of prolonged training. Achievement of the maximum degree of lateralization by the animals finally forming the right-handed group was found to require longer average training periods than was the case for left-handed rats.     

Neurotoxic lesions of the caudate-putamen on a reaching for food task in the rat: acute sensorimotor neglect and chronic qualitative motor impairment follow lateral lesions and improved success follows medial lesions

Reaching for food, or skilled reaching, is used as a test of basal ganglia function in preclinical studies as well as studies of human neurological conditions. Although changes in the end-point measure of success document the effects of neurotoxic cellular damage to the caudate-putamen and its treatment in rodents, there has been no examination of the cause of change in success after neurotoxic lesions of the striatum. This objective was addressed in the present study, in which rats trained to reach for single food pellets with one forelimb, received contralateral quinolinic acid or ibotenic acid lesions of the medial and lateral caudate-putamen. Over 21 postsurgical days, reaching performance was scored for success and qualitative changes in movement elements were examined using frame-by-frame video analysis. In the acute postoperative period, extending over 3 to 4 days, the rats with lateral lesions transported their forelimb and grasped the food, but then ignored the food and did not withdraw their limb to their mouth. After recovery of the withdrawal movement, the rats displayed chronic qualitative impairments in the rotatory movements of aiming, pronating, and supinating the forepaw. Medial quinolinic lesions improved success relative to control rats and did not change qualitative aspects of limb movement. The acute dissociation between transport and withdrawal, the chronic qualitative changes in movement elements, and the differential effect of medial and lateral injury on success, support a complex contribution of the caudate-putamen to skilled reaching that includes sensorimotor neglect, and quantitative and qualitative motoric changes.     

Operant slowing of the extension phase of the reaching movement in rats

Motor learning was studied in rats (n = 8) trained to slow down the forepaw extension while reaching into a narrow tube equipped with an axially moving piston. The photoelectrically monitored velocity of the movement between points P1, P2 and P3 (13.0, 15.1 and 17.3 mm from tube entrance) was evaluated with a laboratory computer which also plotted distributions of the corresponding time intervals and delivered food pellets whenever the time interval between P1 and P2 exceeded a preset threshold value (Group I). The additional condition of attaining P3 was required in Group II. Marked prolongation of the P1-P2 interval required about 20 sessions of 512 reaches in Group I and 27 to 30 sessions in Group II. The rats prolonged the P1-P2 interval in two ways: (a) By generating movements the amplitude of which oscillated around the P2 level and thus exposed the P2 sensor to the slow terminal part of the movement; (b) By true velocity decrease in the middle part (P1-P2) of the movements attaining the level P3. It is concluded that reaching is a highly stereotyped instrumental reaction, the pattern of which is not easily modified by operant conditioning. Substantial slowing (2 times) of the ballistic extension phase of long reaches probably reflects programmed coactivation of the antagonist.     

An analysis of the behavior elicited by stimulation of the dorsal pons in rat

Dorsal pontine intracranial self-stimulation (ICSS) sites were electrically stimulated in rats. Only stimulation-induced oral behavior and not locomotor behavior was observed. The predominant elicited behavior was a fragmentary type of forepaw grooming. In some cases the stimulation-induced forepaw grooming was changed to drinking by the forced presentation of a drinking spout in the perioral region. Neither the dorsal pontine stimulation-induced oral behavior nor the ICSS was disrupted by six-hydroxydopamine lesions of ascending noradrenergic projections from locus coeruleus to widespread forebrain areas. It is suggested that the mesencephalic nucleus of the trigeminal nerve, with its connections to the motor trigeminal nucleus, may mediate dorsal pontine stimulation-induced behavior and ICSS.     

Outsider interference: no role for motor lateralization in determining the strength of avoidance responses during reaching

When reaches are performed toward target objects, the presence of other non-target objects influences kinematic parameters of the reach. A typical observation has been that non-targets positioned ipsilaterally to the acting limb interfere more with the trajectory of the hand than contralateral non-targets. Here, we investigate whether this effect is mediated by motor lateralization or by the relative positioning of the objects with reference to the acting limb. Participants were asked to perform reaches toward physical target objects with their preferred or non-preferred hands while physical non-targets were present in different possible positions in the workspace. We tested both left-handers and right-handers. Our results show that a participant’s handedness does not influence reaching behavior in an obstacle avoidance paradigm. Furthermore, no statistically significant differences between the use of the preferred and non-preferred hand were observed on the kinematic parameters of the reaches. We found evidence that non-targets positioned on the outside of the reaching limb influenced the reaching behavior more strongly than non-targets on the inside. Moreover, the type of movement also appeared to play a role, as reaches that crossed the workspace had a stronger effect on avoidance behavior than reaches that were ‘uncrossed.’ We interpret these results as support for the hypothesis that the avoidance response is determined by keeping a preferred distance between the acting limb in all stages of its reach toward the target and the non-target position. This process is not biased by hand dominance or the hand preference of the actor.     

Environment-specific conditioning produced by electrical stimulation of the lateral hypothalamus

Rats received noncontingent electrical stimulation of the lateral hypothalamus on one side of a place preference apparatus and no stimulation on the other side. Subsequently, when allowed access to both sides, the rats spent more time on the side associated with stimulation. This change in preference was only found in rats receiving stimulation in the side least preferred prior to conditioning trials. It was further shown that the place preference conditioning procedure produces increased locomotor activity. Thus, the place preference obtained was not an artifact produced by a conditioned freezing response. These data suggest that both the reinforcing and activating effects of lateral hypothalamic stimulation may be conditioned to a specific environment. Some methodological problems of the place preference paradigm are discussed.     

An apparent genetic relationship between appetitive and aversive effects of lateral hypothalamic stimulation in the mouse

Three experiments were performed with BALB/c and DBA/2 mice strains implanted in the ventral part of the lateral hypothalamus (LH). Delay times in approach and escape reactions caused by continuous electrical stimulation of the LH were determined in a shuttle box. At most applied current intensities, BALB/c mice triggered and interrupted stimulation more rapidly than did DBA/2 animals. In a second experiment, intracranial self-stimulation behavior (ICSS) triggered by brief (200 msec) stimulation was studied in a lever box. In this experimental situation, the response rate of the BALB/c strain was much higher than that of the DBA/2. Finally, the effects of a fragmented stimulation, reproducing the lever pressing ICSS rhythm were studied in the shuttle box on the same animals. It was seen that BALB/c mice triggered stimulation more rapidly, as in the first experiment, and that they also remained stimulated for a much longer time than DBA/2 at the highest current intensities applied, as in the second experiment. These results suggest that approach responses are related to the onset of stimulation while escape reactions are provoked by the lengthening of the stimulation. A close relationship was seen between the intensity of the approach reaction and that of the escape reaction in the same strain.     

Skilled forelimb movements and unit activity in motor cortex and caudate nucleus in rats

Adult hooded rats were trained to reach for small food pellets into a narrow plexiglass tube and movement of the preferred forelimb was photoelectrically detected. Unit activity was sampled from the motor cortex and caudate nucleus of unrestrained animals with capillary microelectrodes inserted into the brain with a miniature microdrive fixed to a chronically implanted guiding tube. Distribution of isolated spikes during 512 ms before and after the onset of reaching was compiled with a computer. The most striking reaction in the peri-reach histograms was a phasic activity increase starting 64 ms before to 32 ms after the forelimb extension and lasting about 100 ms, which was observed in about 20% neurons (n = 45) in the contralateral motor cortex. This reaction was clearly distinct from tonic excitatory and inhibitory responses starting 200-0 ms before reaching and lasting for several hundred ms. In the contralateral caudate nucleus (n = 62) excitatory and inhibitory responses occurred earlier and were often confined to the pre-extension period. Inhibitory reactions were prevalent in the ipsilateral cortex (n = 52) and caudate (n = 57).It is concluded that the phasic responses in the contralateral motor cortex participate in the actual reaching, whereas the tonic reactions in the contralateral cortex and caudate reflect the auxiliary support mechanisms. Predominantly inhibitory reactions in the ipsilateral hemisphere indicate reduced activity of the centres of the non-preferred forepaw.     

Heat production and motor deficit in rats lesioned in globus pallidus, entopeduncular nucleus and lateral hypothalamus

Oxygen consumption, colonic and interscapular brown adipose tissue temperature were evaluated in four groups of male and four groups of female rats both before and after lesions in different brain regions, and following beta-blocker propranolol administration. Recovery of body weight with varying difficulties in reaching food was also recorded in the injured animals. Groups consisted of rats with bilateral lesions in the entopeduncular nucleus (group EN), rats with bilateral lesions in the globus pallidus (group GP), rats with lateral hypothalamic lesions in the left side and entopeduncular lesion in the right side (group EN-LH), and rats with bilateral lesions in the lateral hypothalamus (group LH). Colonic and brown adipose tissue temperature and oxygen consumption were significantly increased after lesions in rats of groups EN, LH and EN-LH, but not in animals of the GP groups. Similarly, propranolol administration blocked the rise in heat production only in EN, LH and EN-LH animals. No differences were found between sexes. The survival rate was the same in all groups. GP rats recovered body weight earlier than animals injured in the other regions. The difficulty in reaching food was an important factor only in rats damaged in the EN. The results suggest that lateral hypothalamus and entopeduncular nucleus share a common regulatory function of the energy metabolism, while EN lesions induce a motor deficit in addition.     

Amplification and diffusion of manual preference from lateralized practice in children

The effect of lateralized practice on manual preference was investigated in right-handed children. Probing tasks required reaching and grasping a pencil at distinct eccentricities in the right and left hemifields (simple), and its transportation and insertion into a small hole (complex). During practice, the children experienced manipulative tasks different from that used for probing, using the left hand only. Results showed that before practice the children used almost exclusively the right hand in the right hemifield and at the midline position. Following lateralized practice frequency of use of the left hand increased in most lateral positions. A more evident effect of lateralized practice on shift of manual preference was detected in the complex task. Implications for lateralization of behavior in a developmental timescale are discussed on the basis of the proposition of amplification and diffusion of manual preference from lateralized practice.     

Electrical self-stimulation of the mesencephalic central gray area: facilitation by lateral hypothalamic stimulation

Three experiments were performed with BALB/c mice implanted both in the lateral hypothalamus (LH) and the dorsal part of the mesencephalic central gray area (CG). Initially, the effects of a brief electrical stimulation (0.2 sec) of the LH on approach and escape responses produced by continuous stimulation of the dorsal CG, were studied in a shuttle-box. Starting at an intensity of 10 microA, imposed LH stimulation both reduced approach latency and increased escape latency with CG stimulation. In the second and third experiments, the animals were placed in a standard self-stimulation (ICSS) box; depressions of a lever delivered brief electrical stimulations (0.2 sec). During the second experiment, it was observed that the very weak ICSS behavior produced by dorsal CG activation was greatly improved by forced LH stimulation. Finally, in the third experiment, simultaneous ICSS in LH and CG was compared with ICSS in LH alone. When low current intensities were used, simultaneous ICSS in LH and CG was more intense than ICSS in LH alone. These data especially suggest that dorsal CG stimulation has an appetitive component, and consequently that neuronal elements related to the positive reinforcement system are present in the dorsal CG area. Furthermore, the fact that one can obtain interactions between mesencephalic and hypothalamic ICSS is in accordance with the claim that the LH has connections with the CG area.     

Response of medial telencephalic neurons to stimulation in reinforcing sites in the medial forebrain bundle and ventral tegmental area.

Responses of 361 single units recorded extracellularly in various medial telencephalic loci (?2.5 mm from midline) to stimulation in behaviorally-verified, intracranial self-stimulation (ICSS) sites were studied in rats lightly anesthetized with halothane. Trains of 100 Hz stimulation in ICSS sites at behaviorally effective intensities produced widespread effects on telencephalic neurons; 78% showed a short-term response (duration <1.5 sec), a long-term response (duration several sec), or both. Most areas had no single predominant type of response and showed a mixture of ON and OFF short-term responses. Exceptional regions were the superficial layers of cortex, predominantly ON responses, and the lateral septal region, predominantly OFF responses. The responses in most regions were similar to barpressing ICSS in that they directly depended on pulse frequency, i.e., 100 Hz stimulation produced a stronger response than 50 or 25 Hz. The septal region was high in frequency dependent response whereas the globus pallidus and olfactory nuclei were low. Short-term OFF responses were more often frequency dependent than ON responses, particularly those associated with short-latency (?20 msec) spike discharges. Stimulation in two ICSS sites tested on the same neuron produced more mutual OFF responses than mutual ON responses. The results indicate that ICSS has pervasive influences in the telencephalon. Of these influences, the inhibitory types appear to be most consistently related to ICSS behavior.     

A triphasic curve characterizes the retention of lever-pressing behavior rewarded by lateral hypothalamic stimulation during the immediate-post-trial period in rats: implications for a transient-intermediate stage between short- and long-term memory

We investigated the retention of lever-pressing behavior in rats rewarded by lateral hypothalamic (LHT) stimulation. Rats with electrodes implanted into the lateral hypothalamus were trained to press a lever to receive LHT stimulation. More than 90% of rats which had self-stimulated for longer than 30 min retained this behavior when tested 1 or 7 days later, indicating that intracranial self-stimulation (ICSS) produced a stable long-term memory lasting for at least 7 days. Subsequently, we examined retention at shorter ICSS-test intervals. Retention rates were measured 15, 30, 60, 90, 120, 180 or 360 min after the end of a 90-min period of ICSS, using a different group of 15 rats for each interval. Unexpectedly, retention rates in shorter interval tests were lower than those observed after 1 or 7 days. We observed a characteristic fluctuation in retention rates with lower rates at 30 and 180 min, giving a triphasic form to the retention curve with peaks at 15, 90 and 360 min. When a group of rats that had been previously stimulated and shown to have retained the lever-pressing behavior was allowed to re-stimulate a second time, no fluctuations were observed in short-term interval tests. This indicates that the fluctuations in the retention curve immediately after initial ICSS are closely related to the initial acquisition of the memory. Our results support a three-phase model of memory formation that includes a transient-intermediate stage between short- and long-term memory.     

Effects of intracranial reward strength on escape threshold

Rats with implanted monopolar electrodes in the lateral posterior hypothalamus were trained for self-stimulation behavior (ICSS). Rats were allowed to self-stimulate in a two-compartment test chamber. Thirty-eight different electrical stimuli were used to maintain ICSS. In one compartment, a foot shock of increasing voltage was administered. It was observed that the voltage of the foot shock required to elicit an escape response increases during ICSS. This attenuation of aversive state was related to the strength of the reinforcing effect elicited by brain stimulation. The reinforcing effect involves two factors of which only one seems to be responsible of the escape threshold modification.     

Opposite turning behavior in right-handers and non-right-handers suggests a link between handedness and cerebral dopamine asymmetries

The strong right hand preference in humans remains a riddle; no lateralized behavior other than fine finger dexterity relates to it. The relation between handedness and language dominance may be far weaker than currently judged; after all, both right-handers and non-right-handers utilize the left brain for speech. There is, however, a lateralized motor preference in animals, turning behavior, that is strongly associated with hemispheric dopamine (DA) asymmetries. Turning consistently occurs towards the side with less DA. The authors tested 69 right-handers and 24 non-right-handers with a device recording spontaneous turning behavior for 20 hr within 3 days. Findings indicate that right-handers preferred left-sided turning and non-right-handers preferred right-sided turning. This result suggests a link between handedness and DA asymmetries.     

Unilateral striatal grafts induce behavioral and electrophysiological asymmetry in rats with bilateral kainate lesions of the caudate nucleus

Rats (n = 11) with bilateral kainate lesions of the caudate nucleus and subsequent unilateral transplantation of embryonic striatal tissue into the damaged area preferred 4 months later to reach for food with the forepaw contralateral to the graft. No such asymmetry was observed in lesioned, nontransplanted (n = 8) or unoperated (n = 5) control rats. Good integration of the graft with the host brain was indicated by the finding that cortical spreading depression did not enter the lesioned caudate nucleus but did penetrate into the lesioned caudate with the graft almost as regularly as in intact rats. Behavioral asymmetry produced by unilateral grafts in bilaterally lesioned animals reveals the effects of transplantation with more sensitivity than the graft-induced compensation of the asymmetries caused by unilateral lesions.