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Motivational changes in the rat following lesions of the mesencephalic reticular formation
EXPERIMENTAL
NEUROLOGY
Motivational of
11,
334-340
Changes the
in the
Mesencephalic
PAUL ELLEN, ARTHUR Veterans
Administration
(1965)
Center,
Rat
Following
Reticular
S. WILSON,
AND
Formation ERVIN
and University of Mississippi Jackson, Mississippi
Received
September
Lesions
W. POWELL] School
of Medicine
29, 1964
Tegmental lesions produced high as well as low terminal response rates in rats trained on a fixed-interval reinforcement schedule. This diversity of effect on a measure reflecting motivational or drive level points to the complexity of reticular influence on mechanisms of motivation and suggests that this influence is the resultant of mutually opposing processes. Finally, none of the lesions including those restricted to the red nucleus impaired temporal discrimination. Introduction
We previously found that various aspects of performance on a fixedinterval reinforcement schedule may be differentially affected by CNS lesions. When the lesions involved primarily rhinencephalic structures (septum, hippocampus and mamillary body) the temporal distribution of responses, indicative of the acquisition of a temporal discrimination, was unimpaired (3-S). The terminal response rate, a measure of the motivational or drive level in the performance (14), was either increased or decreased depending upon the particular structure involved. Lesions involving the zona incerta, however, impaired the acquisition of the temporal discrimination without having any significant effect on the response rate (5). Since rhinencephalic and extrapyramidal structures have reciprocal connections with the reticular formation of the midbrain (9-l 1)) the known anatomical projections combined with the behavioral results cited would lead to the expectation that discrete lesions in the midbrain tegmentum might affect either or both of these aspects of the fixed-interval behavior. The present study was done to explore the nature of the changes in fixed-interval behavior following midbrain tegmental lesions. 1 Supported
in part
by USPHS
Grant
MH-07802-01. 334
RETICULAR
FORMATION
335
Procedure
After preliminary training in bar-pressing for a 0.45mg food pellet, fourteen Long-Evans hooded rats approximately 120 days old were prepared with electrolytic lesions in the midbrain tegmentum. The lesions were stereotaxically oriented with the placements set l-2 mm anterior to the interaural line, 6-8 mm below the skull surface, and varying 0.5-2.0 mm laterally from the midline. Surgery was performed under Nembutal anesthesia (0.5 mg/lOO mg, body weight) and the lesions were produced by passing a 2-mamp current for 10 set through a 350-p stainless steel electrode insulated except at the tip. On the day following surgery, barpressing on a continuous reinforcement schedule was reinstituted and carried on for 6 postoperative days. This was to allow acute postoperative effects to dissipate prior to the start of training on the fixed-interval schedule on the seventh postoperative day. In a fixed-interval schedule, the delivery of reinforcement is dependent on the animal making a response after a fixed period of time has elapsed since the previous reinforcement (6). The schedule used in the present study required that one minute elapse since the previous reward. Training on this schedule was continued for 10 days with each animal receiving 150 reinforcements per day. At the conclusion of training, the animals were killed, the brains fixed in formalin, and serial frozen sections made. Lesion location and size was determined by the method described by Powell (12), using unstained sections projected onto the back of a Polaroid film. Subsequently all slides were stained with cresyl violet for additional study. Results
The point of maximum involvement of the fourteen lesions as they appeared in various rostra1 to caudal levels of the midbrain tegmentum is shown in Fig. 1. It may be noted from these sections that five of the placements (414, 614, 213, 315 and 71.5) incriminated a major part of the red nucleus unilaterally. The remaining lesions were distributed from the edge of the central gray laterally into the diffuse or general tegmentum of the midbrain. Motivational Eflects. The effects of the lesions on the motivationa component of interval behavior as revealed by the terminal response rate (i.e., the rate in the last lo-set period prior to the availability of reinforcement) is presented in Table 1. It will be noted there is an increase
336
ELLEN,
FIG. 1. Midbrain lesions: actual lesions. Solid black, lesions resulting in reduced nucleus. Abbreviations: Bi,
WILSON,
AND
POWELL
A, rostral; B, middle; C, caudal; D, E, F, examples of lesions resulting in augmented terminal rate; stipling, terminal rate; double crosshatching, lesions of the red brachium of inferior colliculus; Cg, central gray; Cm,
RETICULAR
337
FORMATION
in response rate from day 1 to day 10 for all animals as would be expected from previous work (3, 4). The point of primary interest, however, is the fact that a wide variability in the daily terminal response rates exists among the animals. Considering the final day of training for example, response rates range between 0.26 and 1.48 responses per sec. Anatomical TERMINAL
Days RatNo. 214 514 813 614’” 714 613 814 715a 31P 414a 314 113 213a 713
RESPONSE
TABLE RATE:
1 RESPONSES
PER SECOND
I
2
3
4
5
6
8
9
10
0.60 0.56 0.63 0.97 0.37 0.79 0.43 0.38 0.40 0.21 0.25 0.50 0.32 0.18
1.06 1.20 0.60 1.30 0.56
1.12 1.52 0.95 1.65 0.56 1.72 1.06 0.41 0.55 0.33 0.30 0.45 0.26 0.14
1.27 1.68 1.25 1.76 1.04 1.78 1.01 0.75 0.43 0.33 0.28 0.55 0.35 0.21
1.03 1.56 1.02 1.58 0.84 1.88 0.89 0.57 0.52 0.29 0.18 0.67 0.29 0.18
1.21 1.57 0.98 1.43 1.09 2.16 0.87 0.53 0.73 0.46 0.16 0.59 0.40 0.34
1.05 1.39 0.82 1.53 1.85 1.92 1.38 0.62 0.76 0.57 0.3 1 0.44 0.41 0.25
1.31 0.92 1.23 1.18 0.63
1.56 1.56 1.25 1.24 1.03
1.92
1.11
0.68 0.81 0.85 0.56 0.50 0.39 0.62 0.47
0.92 0.70 1.06 0.64 0.63 0.49 0.45 0.30
1.48 1.46 1.19 1.17 1.14 1.08 0.98 0.87 0.84 0.65 0.54 0.46 0.39 0.26
1.10
0.96 0.48 0.47 0.41 0.25 0.46 0.29 0.18
7
Mean
0.47
0.67
0.79
0.91
0.82
0.89
0.95
0.86
0.92
0.89
SD.
0.22
0.36
0.52
0.55
0.53
0.54
0.55
0.41
0.40
0.38
Q Lesions
predominantly
in the red nucleus.
correlations of these results do not resolve the behavioral variability found. When the response rates are correlated with lesion placements (Fig. l), lesions which led to high response rates (> 1 response/set) have a considerable overlap with lesions which resulted in a moderate to low response rate (< 1 response/set). Temporal Discrimination. The temporal distribution of responses on the final day of training on the fixed-interval schedule is shown in Fig. 2. In this figure, the 1-min fixed interval was subdivided into subintervals middle cerebellar peduncle; Cp, cerebral peduncle ; Cs, superior cerebellar peduncle; Gm, medial geniculate body; 11, inferior colliculus; Ip, interpeduncular nucleus; MC, medial longitudinal fasciculus; Ml, medial lemniscus; Mp, mamillary peduncle; Pn, pons; Py, pyramidal tract; Rf, reticular formation; Rn, red nucleus; SC, superior colliculus ; Sh, spinothalamic tract; Sn, substantia nigra.
338
ELLEN,
WILSON,
AND
POWELL
of 10 set each and the percentage of the total responses which occurred in each subinterval prior to and for 10 set after 1 min are plotted. It may be seen from Fig. 2a that on the average the bar-pressing behavior has become correlated with the temporal occurrence of reinforcement. Immediately following reinforcement relatively few bar-presses occur, while as the time for the next reinforcement approaches the frequency of the barpressing increases. This temporal distribution of bar-pressing behavior is
60
a.
Reticular
Formation
I
b.
Sub-
Intervals
Red
Nucleus
50 40 30 20 IO 0
1234567
1234567 IO Set
FIG. 2. Temporal discrimination on final day of fixed-interval distribution for all animals. b. Response distribution for only lesions were confined primarily to the red nucleus.
training. a. Response those animals whose
characteristic of what occurs with normal nonoperated rats and has been used as evidence of the acquisition of a temporal discrimination in a fixedinterval schedule (4, 6, 14). Of especial interest is the similarity to the over-all group plot (Fig. 2a), of the temporal distribution of responses for the five animals whose lesions were primarily in the red nucleus (Fig. 2b). Discussion
The finding that some of the tegmental lesions produced low response rates is in accord with the results of Ehrlich’s study (2). She found that bilateral lesions of the tegmentum decreased bar-pressing for food or water, and suggested that this effect might have resulted from a slight decrease in arousal level. However, our observation that some of the tegmental lesions produced response rates greater than 1 per set is not explicable from this point of view. A response rate greater than 1 per set is higher
RETICULAR
FORMATION
339
than that emitted by nonoperated animals and closely approximates that of animals with septal lesions (3, 4). This suggests that a system other than merely an arousal or excitatory one may have been implicated by our lesions. Moreover, the divergency in response rate following overlapping lesions in the tegmentum suggests that the behavioral end product (response rate) resulting from large tegmental lesions reflects an interaction of mutually opposing processes. Large lesions of the tegmentum have generally revealed the excitatory nature of reticular function (8). In our study the larger lesions (Table 1: 314 and 414) produced moderate to low response rates. It remains for further investigation to determine whether the interactive nature of reticular function can be resolved by smaller lesions. In this regard, the differential projection topography to the tegmentum from limbic structures assumes considerable importance. In particular, septum tends to project to more ventral aspects of the tegmentum ( 11) while hippocampus tends to project to more dorsal aspects (10). We have previously shown that lesions in the septum and hippocampus have opposite effects on terminal response rates (4). It is not unreasonable to suppose that these differential relations also exist at the tegmental level and can be differentiated through the use of small lesions. In this connection, recent findings of Glickman et ~2. (7) are of interest. They found that ventral tegmental lesions (between the lateral tips of the central gray and the dorsal ventral level of the red nuclei) produced an increase in exploratory activity while dorsal tegmental lesions (from the superior colliculi through the dorsal tegmenturn) produced a decrease in such activity. However, since they used bilateral lesions, the dorsal-ventral distinction with respect to the behavioral consequences of tegmental lesions may not be applicable when unilateral lesions are involved. This would be especially true if certain functional deficits required qualitative combinations of specific anatomical structures. Such system structures are compactly arranged in the confines of the mesencephalon. Finally, in view of our earlier report concerning the impairment in the acquisition of a temporal discrimination following lesions in the zona incerta (5) it was expected that a defect in temporal discrimination might be observed with lesions in the red nucleus since this structure is one of the downstream projections of the extrapyramidal system (1). However, no impairment in the acquisition of the temporal discrimination was found following lesions in the red nucleus or general tegmentum. Since this measure reflects the discriminative or cognitive dimension of the fixed-
340
ELLEN,
interval nificant strongly involved neuraxis
WILSON,
AND
POWELL
behavior (4) it is unlikely that the lesions produced any sigalterations in attention or adaptation (13). Rather these data indicate that the structures mediating the behavioral processes in temporal discrimination are located more rostrally in the than at the midbrain level. References
1. 2. 3. 4. 5. 6. 7. 8.
9. 10. 11. 12.
13. 14.
DENNY-BROWN, D. 1962. “The Basal Ganglia and Their Relation to Disorders of Movement.” Oxford Univ. Press, London and New York. EHFZICH, A. 1963. Effects of tegmental lesions on motivated behavior in rats. J. Camp. Physiol. Psychol. 56: 390-396. ELLEN, P., and E. W. POWELL. 1962. Effects of septal lesions on behavior generated by positive reinforcement. ~%tpt~. Neuvol. 6: l-11. ELLEN, P., and E. W. POWELL. 1962. Temporal discrimination in rats with rhinencephalic lesions. Exptl. Neurol. 6: 538-547. ELLEN, P., and E. W. POWELL. 1963. Timing behavior after lesions of zona incerta and mamillary body. Science 141: 828-830. FERSTER, C. B., and B. F. SKINNER. 1957. “Schedules of Reinforcement.” Appleton, New York. GLICKMAN, S. E., R. W. SROGES, and J. HUNT. 1964. Brain lesions and locomotor exploration in the albino rat. J. Comp. Physiol. Psychol. 58: 93-100. LINDSLEY, D. B., L. H. SCHREINER, W. B. KNOWLES, and H. W. MAGOUN. 1950. Behavioral and EEG changes following chronic brain stem lesions in the cat. Electroencephalog. Clin. Neurophysiol. 2: 483-498. MOREST, D. K. 1961. Connexions of the dorsal tegmental nucleus in rat and rabbit. J. Anat. 93: 229-246. NAUTA, W. J. H. 1958. Hippocampal projections and related neural pathways to the midbrain in the cat. Brain 81: 319-340. POWELL, E. W. 1963. Septal efferents revealed by axonal degeneration in the rat. Exptl. Neural. 8: 406-422. POWELL, E. W. 1964. A rapid method of intracranial electrode localization using unstained frozen sections. Electroencephalog. Clin. Neurophysiol. 17: 432-434. SPRAGUE, J. M., W. W. CHAMBERS, and E. STELLAR. 1961. Attentive, affective, and adaptive behavior in the cat. Science 133: 165-173. WEISS, B., and W. MOORE. 1956. Drive level as a factor in the distribution of responses in fixed-interval reinforcement. J. Exptl. Psychol. 52: 82-84.
NEUROLOGY
Motivational of
11,
334-340
Changes the
in the
Mesencephalic
PAUL ELLEN, ARTHUR Veterans
Administration
(1965)
Center,
Rat
Following
Reticular
S. WILSON,
AND
Formation ERVIN
and University of Mississippi Jackson, Mississippi
Received
September
Lesions
W. POWELL] School
of Medicine
29, 1964
Tegmental lesions produced high as well as low terminal response rates in rats trained on a fixed-interval reinforcement schedule. This diversity of effect on a measure reflecting motivational or drive level points to the complexity of reticular influence on mechanisms of motivation and suggests that this influence is the resultant of mutually opposing processes. Finally, none of the lesions including those restricted to the red nucleus impaired temporal discrimination. Introduction
We previously found that various aspects of performance on a fixedinterval reinforcement schedule may be differentially affected by CNS lesions. When the lesions involved primarily rhinencephalic structures (septum, hippocampus and mamillary body) the temporal distribution of responses, indicative of the acquisition of a temporal discrimination, was unimpaired (3-S). The terminal response rate, a measure of the motivational or drive level in the performance (14), was either increased or decreased depending upon the particular structure involved. Lesions involving the zona incerta, however, impaired the acquisition of the temporal discrimination without having any significant effect on the response rate (5). Since rhinencephalic and extrapyramidal structures have reciprocal connections with the reticular formation of the midbrain (9-l 1)) the known anatomical projections combined with the behavioral results cited would lead to the expectation that discrete lesions in the midbrain tegmentum might affect either or both of these aspects of the fixed-interval behavior. The present study was done to explore the nature of the changes in fixed-interval behavior following midbrain tegmental lesions. 1 Supported
in part
by USPHS
Grant
MH-07802-01. 334
RETICULAR
FORMATION
335
Procedure
After preliminary training in bar-pressing for a 0.45mg food pellet, fourteen Long-Evans hooded rats approximately 120 days old were prepared with electrolytic lesions in the midbrain tegmentum. The lesions were stereotaxically oriented with the placements set l-2 mm anterior to the interaural line, 6-8 mm below the skull surface, and varying 0.5-2.0 mm laterally from the midline. Surgery was performed under Nembutal anesthesia (0.5 mg/lOO mg, body weight) and the lesions were produced by passing a 2-mamp current for 10 set through a 350-p stainless steel electrode insulated except at the tip. On the day following surgery, barpressing on a continuous reinforcement schedule was reinstituted and carried on for 6 postoperative days. This was to allow acute postoperative effects to dissipate prior to the start of training on the fixed-interval schedule on the seventh postoperative day. In a fixed-interval schedule, the delivery of reinforcement is dependent on the animal making a response after a fixed period of time has elapsed since the previous reinforcement (6). The schedule used in the present study required that one minute elapse since the previous reward. Training on this schedule was continued for 10 days with each animal receiving 150 reinforcements per day. At the conclusion of training, the animals were killed, the brains fixed in formalin, and serial frozen sections made. Lesion location and size was determined by the method described by Powell (12), using unstained sections projected onto the back of a Polaroid film. Subsequently all slides were stained with cresyl violet for additional study. Results
The point of maximum involvement of the fourteen lesions as they appeared in various rostra1 to caudal levels of the midbrain tegmentum is shown in Fig. 1. It may be noted from these sections that five of the placements (414, 614, 213, 315 and 71.5) incriminated a major part of the red nucleus unilaterally. The remaining lesions were distributed from the edge of the central gray laterally into the diffuse or general tegmentum of the midbrain. Motivational Eflects. The effects of the lesions on the motivationa component of interval behavior as revealed by the terminal response rate (i.e., the rate in the last lo-set period prior to the availability of reinforcement) is presented in Table 1. It will be noted there is an increase
336
ELLEN,
FIG. 1. Midbrain lesions: actual lesions. Solid black, lesions resulting in reduced nucleus. Abbreviations: Bi,
WILSON,
AND
POWELL
A, rostral; B, middle; C, caudal; D, E, F, examples of lesions resulting in augmented terminal rate; stipling, terminal rate; double crosshatching, lesions of the red brachium of inferior colliculus; Cg, central gray; Cm,
RETICULAR
337
FORMATION
in response rate from day 1 to day 10 for all animals as would be expected from previous work (3, 4). The point of primary interest, however, is the fact that a wide variability in the daily terminal response rates exists among the animals. Considering the final day of training for example, response rates range between 0.26 and 1.48 responses per sec. Anatomical TERMINAL
Days RatNo. 214 514 813 614’” 714 613 814 715a 31P 414a 314 113 213a 713
RESPONSE
TABLE RATE:
1 RESPONSES
PER SECOND
I
2
3
4
5
6
8
9
10
0.60 0.56 0.63 0.97 0.37 0.79 0.43 0.38 0.40 0.21 0.25 0.50 0.32 0.18
1.06 1.20 0.60 1.30 0.56
1.12 1.52 0.95 1.65 0.56 1.72 1.06 0.41 0.55 0.33 0.30 0.45 0.26 0.14
1.27 1.68 1.25 1.76 1.04 1.78 1.01 0.75 0.43 0.33 0.28 0.55 0.35 0.21
1.03 1.56 1.02 1.58 0.84 1.88 0.89 0.57 0.52 0.29 0.18 0.67 0.29 0.18
1.21 1.57 0.98 1.43 1.09 2.16 0.87 0.53 0.73 0.46 0.16 0.59 0.40 0.34
1.05 1.39 0.82 1.53 1.85 1.92 1.38 0.62 0.76 0.57 0.3 1 0.44 0.41 0.25
1.31 0.92 1.23 1.18 0.63
1.56 1.56 1.25 1.24 1.03
1.92
1.11
0.68 0.81 0.85 0.56 0.50 0.39 0.62 0.47
0.92 0.70 1.06 0.64 0.63 0.49 0.45 0.30
1.48 1.46 1.19 1.17 1.14 1.08 0.98 0.87 0.84 0.65 0.54 0.46 0.39 0.26
1.10
0.96 0.48 0.47 0.41 0.25 0.46 0.29 0.18
7
Mean
0.47
0.67
0.79
0.91
0.82
0.89
0.95
0.86
0.92
0.89
SD.
0.22
0.36
0.52
0.55
0.53
0.54
0.55
0.41
0.40
0.38
Q Lesions
predominantly
in the red nucleus.
correlations of these results do not resolve the behavioral variability found. When the response rates are correlated with lesion placements (Fig. l), lesions which led to high response rates (> 1 response/set) have a considerable overlap with lesions which resulted in a moderate to low response rate (< 1 response/set). Temporal Discrimination. The temporal distribution of responses on the final day of training on the fixed-interval schedule is shown in Fig. 2. In this figure, the 1-min fixed interval was subdivided into subintervals middle cerebellar peduncle; Cp, cerebral peduncle ; Cs, superior cerebellar peduncle; Gm, medial geniculate body; 11, inferior colliculus; Ip, interpeduncular nucleus; MC, medial longitudinal fasciculus; Ml, medial lemniscus; Mp, mamillary peduncle; Pn, pons; Py, pyramidal tract; Rf, reticular formation; Rn, red nucleus; SC, superior colliculus ; Sh, spinothalamic tract; Sn, substantia nigra.
338
ELLEN,
WILSON,
AND
POWELL
of 10 set each and the percentage of the total responses which occurred in each subinterval prior to and for 10 set after 1 min are plotted. It may be seen from Fig. 2a that on the average the bar-pressing behavior has become correlated with the temporal occurrence of reinforcement. Immediately following reinforcement relatively few bar-presses occur, while as the time for the next reinforcement approaches the frequency of the barpressing increases. This temporal distribution of bar-pressing behavior is
60
a.
Reticular
Formation
I
b.
Sub-
Intervals
Red
Nucleus
50 40 30 20 IO 0
1234567
1234567 IO Set
FIG. 2. Temporal discrimination on final day of fixed-interval distribution for all animals. b. Response distribution for only lesions were confined primarily to the red nucleus.
training. a. Response those animals whose
characteristic of what occurs with normal nonoperated rats and has been used as evidence of the acquisition of a temporal discrimination in a fixedinterval schedule (4, 6, 14). Of especial interest is the similarity to the over-all group plot (Fig. 2a), of the temporal distribution of responses for the five animals whose lesions were primarily in the red nucleus (Fig. 2b). Discussion
The finding that some of the tegmental lesions produced low response rates is in accord with the results of Ehrlich’s study (2). She found that bilateral lesions of the tegmentum decreased bar-pressing for food or water, and suggested that this effect might have resulted from a slight decrease in arousal level. However, our observation that some of the tegmental lesions produced response rates greater than 1 per set is not explicable from this point of view. A response rate greater than 1 per set is higher
RETICULAR
FORMATION
339
than that emitted by nonoperated animals and closely approximates that of animals with septal lesions (3, 4). This suggests that a system other than merely an arousal or excitatory one may have been implicated by our lesions. Moreover, the divergency in response rate following overlapping lesions in the tegmentum suggests that the behavioral end product (response rate) resulting from large tegmental lesions reflects an interaction of mutually opposing processes. Large lesions of the tegmentum have generally revealed the excitatory nature of reticular function (8). In our study the larger lesions (Table 1: 314 and 414) produced moderate to low response rates. It remains for further investigation to determine whether the interactive nature of reticular function can be resolved by smaller lesions. In this regard, the differential projection topography to the tegmentum from limbic structures assumes considerable importance. In particular, septum tends to project to more ventral aspects of the tegmentum ( 11) while hippocampus tends to project to more dorsal aspects (10). We have previously shown that lesions in the septum and hippocampus have opposite effects on terminal response rates (4). It is not unreasonable to suppose that these differential relations also exist at the tegmental level and can be differentiated through the use of small lesions. In this connection, recent findings of Glickman et ~2. (7) are of interest. They found that ventral tegmental lesions (between the lateral tips of the central gray and the dorsal ventral level of the red nuclei) produced an increase in exploratory activity while dorsal tegmental lesions (from the superior colliculi through the dorsal tegmenturn) produced a decrease in such activity. However, since they used bilateral lesions, the dorsal-ventral distinction with respect to the behavioral consequences of tegmental lesions may not be applicable when unilateral lesions are involved. This would be especially true if certain functional deficits required qualitative combinations of specific anatomical structures. Such system structures are compactly arranged in the confines of the mesencephalon. Finally, in view of our earlier report concerning the impairment in the acquisition of a temporal discrimination following lesions in the zona incerta (5) it was expected that a defect in temporal discrimination might be observed with lesions in the red nucleus since this structure is one of the downstream projections of the extrapyramidal system (1). However, no impairment in the acquisition of the temporal discrimination was found following lesions in the red nucleus or general tegmentum. Since this measure reflects the discriminative or cognitive dimension of the fixed-
340
ELLEN,
interval nificant strongly involved neuraxis
WILSON,
AND
POWELL
behavior (4) it is unlikely that the lesions produced any sigalterations in attention or adaptation (13). Rather these data indicate that the structures mediating the behavioral processes in temporal discrimination are located more rostrally in the than at the midbrain level. References
1. 2. 3. 4. 5. 6. 7. 8.
9. 10. 11. 12.
13. 14.
DENNY-BROWN, D. 1962. “The Basal Ganglia and Their Relation to Disorders of Movement.” Oxford Univ. Press, London and New York. EHFZICH, A. 1963. Effects of tegmental lesions on motivated behavior in rats. J. Camp. Physiol. Psychol. 56: 390-396. ELLEN, P., and E. W. POWELL. 1962. Effects of septal lesions on behavior generated by positive reinforcement. ~%tpt~. Neuvol. 6: l-11. ELLEN, P., and E. W. POWELL. 1962. Temporal discrimination in rats with rhinencephalic lesions. Exptl. Neurol. 6: 538-547. ELLEN, P., and E. W. POWELL. 1963. Timing behavior after lesions of zona incerta and mamillary body. Science 141: 828-830. FERSTER, C. B., and B. F. SKINNER. 1957. “Schedules of Reinforcement.” Appleton, New York. GLICKMAN, S. E., R. W. SROGES, and J. HUNT. 1964. Brain lesions and locomotor exploration in the albino rat. J. Comp. Physiol. Psychol. 58: 93-100. LINDSLEY, D. B., L. H. SCHREINER, W. B. KNOWLES, and H. W. MAGOUN. 1950. Behavioral and EEG changes following chronic brain stem lesions in the cat. Electroencephalog. Clin. Neurophysiol. 2: 483-498. MOREST, D. K. 1961. Connexions of the dorsal tegmental nucleus in rat and rabbit. J. Anat. 93: 229-246. NAUTA, W. J. H. 1958. Hippocampal projections and related neural pathways to the midbrain in the cat. Brain 81: 319-340. POWELL, E. W. 1963. Septal efferents revealed by axonal degeneration in the rat. Exptl. Neural. 8: 406-422. POWELL, E. W. 1964. A rapid method of intracranial electrode localization using unstained frozen sections. Electroencephalog. Clin. Neurophysiol. 17: 432-434. SPRAGUE, J. M., W. W. CHAMBERS, and E. STELLAR. 1961. Attentive, affective, and adaptive behavior in the cat. Science 133: 165-173. WEISS, B., and W. MOORE. 1956. Drive level as a factor in the distribution of responses in fixed-interval reinforcement. J. Exptl. Psychol. 52: 82-84.