Normal Drosophila learn to avoid an odorant associated with electric\r\nshock. This dissertation describes the isolation of two x-linked\r\nmutants that fail to display this learning, in spite of being able to\r\nsense the odorants and electric shock. The mutants are proved to be\r\nalleles of one gene, and are named dunce1 and dunce2. The finding that\r\ndunce2 females are sterile led to the discovery that the dunce gene was\r\nindependently known in two other laboratories.
\r\n\r\nKiger, Davis, and Golanty of the University of California at Davis\r\nfind (one) that normal Drosophila have two forms (I and II) of soluble\r\ncyclic AMP phosphodiesterase, differing in molecular weight and other\r\nproperties; (two) that a gene appearing to control form II is included\r\nwithin chromosomal bands 3D3 and 3D4; and (three) that females with\r\nhomozygous deficiency of these two bands are sterile. Mohler of the\r\nUniversity of Iowa isolated 225 x-linked female-sterile mutants. Among\r\nthese Davis and Kiger found two that map within 3D3 and 3D4 and lack\r\nthe form II of soluble cyclic AMP phosphodiesterase.
\r\n\r\nThe two mutants of Mohler learn poorly. They do not complement\r\ndunce1 or dunce2 in learning nor dunce2 in fertility, and therefore are\r\nalleles of the dunce gene. Mapping of learning with genetic deficiencies\r\nand duplications places dunce1 and dunce2 within region 3D3 and 3D4.\r\nFemales with homozygous deficiency of five adjacent bands, including\r\nthese two, are viable and vigorous, but learn poorly and are sterile.
\r\n\r\nThe soluble cyclic AMP phosphodiesterase II is inactive or absent\r\nin homogenates of dunce1 and dunce2 flies. In addition, cyclic AMP\r\nlevels are elevated in the dunce mutants, as expected if cyclic AMP\r\nphosphodiesterase activity is deficient.
\r\n\r\nIt is concluded that the dunce gene of normal Drosophila has functions\r\nin olfactory learning performance, reproduction, and cyclic AMP metabolism.\r\nRecent work with other organisms has suggested that cyclic AMP\r\nmay be intimately involved in mechanisms of learning; the dunce mutant\r\nshould prove helpful in testing this.
", "doi": "10.7907/k8cd-wk36", "publication_date": "1980", "thesis_type": "phd", "thesis_year": "1980" }, { "id": "thesis:14432", "collection": "thesis", "collection_id": "14432", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11202021-011429389", "primary_object_url": { "basename": "RAM_JL_1974.pdf", "content": "final", "filesize": 74580335, "license": "other", "mime_type": "application/pdf", "url": "/14432/1/RAM_JL_1974.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Effects of High K\u207a Media on Leucine Incorporation into Aplysia Nervous Tissue", "author": [ { "family_name": "Ram", "given_name": "Jeffrey Lewis", "clpid": "Ram-Jeffrey-Lewis" } ], "thesis_advisor": [ { "family_name": "Strumwasser", "given_name": "Felix", "clpid": "Strumwasser-F" } ], "thesis_committee": [ { "family_name": "Strumwasser", "given_name": "Felix", "clpid": "Strumwasser-F" }, { "family_name": "Olds", "given_name": "James", "clpid": "Olds-J" }, { "family_name": "Attardi", "given_name": "Giuseppe", "clpid": "Attardi-G" }, { "family_name": "Russell", "given_name": "Richard L.", "clpid": "Russell-R-L" }, { "family_name": "Mitchell", "given_name": "Herschel K.", "clpid": "Mitchell-H-K" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "To study possible coupling between membrane polarization and protein synthesis, elevated external K+ levels were used to depolarize the cell membranes in isolated Aplysia californica parieto-visceral ganglia (PVG). The effect of this treatment on the incorporation of labeled leucine into proteins in the ganglion was analyzed on sodium dodecyl sulfate polyacrylamide gels. PVGs were preincubated 3 hours and then incubated 4 hours in either control medium (14C-leucine, 10 mM [ K+]) or experimental medium (3H-leucine, 10 + x mM [K+] with equimolar [Na+] reduction). These were homogenized together, separated into aqueous soluble and aqueous insoluble fractions, and run on gels.
\r\n\r\nIn the aqueous soluble fraction of the PVG High [K+] (90-110 mM [K+]} caused relative increases in incorporation in distinct peaks at 50K (K = 1000 daltons) and 40K. The larger peak, at 50K, was studied further.
\r\n\r\nThe relative increase at 50K occurred when 14c-leucine (instead of the usual 3H-leucine) was incorporated in High [K+]. The relative increase at 50K did not occur (1) when [K+] was raised to only 50 mM; (2) when [Na+] was reduced by 80 mM, and tris+ (HCl to neutralize) was substituted instead of K+; (3) in pleura-visceral connective (PVC) nerve; and (4) in the aqueous insoluble fraction of the PVG.
\r\n\r\nThe effect of High [K+] on incorporation into the giant cell (R2) of the PVG was examined by first labeling the PVG in control medium, rinsing it, and then labeling it in experimental medium. High [K+] in the experimental medium caused a significant relative increase at 50K in whole PVGs, half PVGs, and R2s dissected from the PVG following incubation. The results in R2 were marred by great variability in the control patterns.
\r\n\r\nAutoradiography of identified cells (R2 and R15) dissected from PVGs labeled with 3H-leucine in normal [K+] showed that contaminating cells {mostly glia), which always adhere to such dissected cells, generally account for less than 20% of the total incorporated formalin-fixed label. This contamination is large enough so that a glial origin of the High [K+] effect on incorporation at 50K cannot be positively excluded. However, the presence of this effect in dissected R2s and its absence in PVC nerves, which contain axons, glia, and connective tissue, but no nerve cell bodies, lend support to the notion that the effect is neuronal in origin.
\r\n\r\nHigh [K+] caused a reduction of approximately SO% in total incorporation into both aqueous soluble and aqueous insoluble proteins of the PVG. Similar decreases of 35% were seen in dissected R2s. [Na+] reduction (by 80 mM, tris+ substitution) had no significant effect on total incorporation (measured only in the aqueous soluble fraction of the PVG). High [K+] caused a reduction of approximately 85% in total incorporation into PVC nerve. Autoradiography of the nerve showed that this reduction occurred in both the connective tissue sheath and the axonal-glial region. High [K+] caused no significant change in non-volatile TCA soluble label in either the ganglion or the nerve.
\r\n\r\nOther effects of High [K+] on the PVG: (1) a small (not large enough to have caused the relative increase at 50K) decrease in the relative amount of label in the aqueous soluble, TCA insoluble fraction compared to the aqueous insoluble fraction, and (2) a relative decrease in incorporation in higher molecular weight peptides compared to lower molecular weight peptides in both aqueous soluble and aqueous insoluble fractions.
\r\n\r\nThese results suggest, but do not prove, that High [K+] caused an increase in the synthesis of a neuronal peptide of approximately 50,000 daltons molecular weight. The possibility that this peptide may be a tubulin subunit is briefly discussed.
", "doi": "10.7907/qtf0-tz26", "publication_date": "1974", "thesis_type": "phd", "thesis_year": "1974" }, { "id": "thesis:10677", "collection": "thesis", "collection_id": "10677", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02062018-101121529", "type": "thesis", "title": "Unit Activity in the Hypothalamus and Striatum of the Rat During Learning", "author": [ { "family_name": "Linseman", "given_name": "Mary Ann Monica", "clpid": "Linseman-Mary-Ann-Monica" } ], "thesis_advisor": [ { "family_name": "Olds", "given_name": "James", "clpid": "Olds-J" } ], "thesis_committee": [ { "family_name": "Olds", "given_name": "James", "clpid": "Olds-J" }, { "family_name": "Van Harreveld", "given_name": "Anthonie", "clpid": "Van-Harreveld-A" }, { "family_name": "Strumwasser", "given_name": "Felix", "clpid": "Strumwasser-F" }, { "family_name": "Owen", "given_name": "Ray David", "clpid": "Owen-R-D" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "Unit activity was recorded from the hypothalamus and striatum\r\nof 80 freely moving rats during an appetitive classical conditioning \r\nsituation. Responses to auditory stimuli were observed from 118\r\nunits before and during a conditioning procedure in which presentation\r\nof food occurred one second after the onset of an auditory stimulus.\r\nA large proportion of units (111) showed changed responses to the CS \r\nduring conditioning. Only 8 of these, however, showed new conditioned \r\nresponses of the very shortest latency measured, 20 msec. after CS \r\nonset. These were interpreted as likely sites of rerouting of the stimulus \r\ninformation within the brain as a result of learning. They \r\nwere located largely near the intersection of hypothalamic and striatal \r\nstructures. A transient increase in rate of background firing over \r\ntrials was recorded following the onset of conditioning among hypo\u00adthalamic \r\nunits, suggesting they may temporarily represent a dynamic trace of the \r\nnew learning. No significant differences were found between areas \r\nstudied in order of appearance over trials of the conditioned responses. \r\nHowever, as a group, the conditioned responses studied here, appeared \r\nsignificantly earlier than a group of cortical neurons studied under \r\nsimilar conditions. There was greater generalization of response \r\nto the CS- by units of the basal ganglia than other areas, suggesting \r\nthey may be of importance in inhibition of response to the CS-.\r\n\r\n", "doi": "10.7907/9BAS-1713", "publication_date": "1973", "thesis_type": "phd", "thesis_year": "1973" }, { "id": "thesis:11121", "collection": "thesis", "collection_id": "11121", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07132018-093853708", "primary_object_url": { "basename": "Gordon_HW_1973.pdf", "content": "final", "filesize": 71604236, "license": "other", "mime_type": "application/pdf", "url": "/11121/1/Gordon_HW_1973.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Verbal and Non-Verbal Cerebral Processing in Man for Audition", "author": [ { "family_name": "Gordon", "given_name": "Harold William", "clpid": "Gordon-Harold-William" } ], "thesis_advisor": [ { "family_name": "Sperry", "given_name": "Roger Wolcott", "clpid": "Sperry-R-W" } ], "thesis_committee": [ { "family_name": "Benzer", "given_name": "Seymour", "clpid": "Benzer-S" }, { "family_name": "Fender", "given_name": "Derek H.", "clpid": "Fender-D-H" }, { "family_name": "Olds", "given_name": "James", "clpid": "Olds-J" }, { "family_name": "Van Harreveld", "given_name": "Anthonie", "clpid": "Van-Harreveld-A" }, { "family_name": "Sperry", "given_name": "Roger Wolcott", "clpid": "Sperry-R-W" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "Hemispheric asymmetries were investigated with various auditory techniques in several groups of subjects. The first study was a dichotic listening experiment in which two separate musical chords were presented simultaneously one to each ear of right-handed males. The subjects were required to listen to the chord stimuli and then recognize them from a multiple choice of four chords heard immediately following the dichotic presentation. More chords were recognized from the left ear than from the right implying right cerebral dominance for this task. In a similar test, dichotic presentation of melodies showed no difference between the ears. It was hypothesized that the subjects in this case were identifying the tune segments on the basis of rhythmic rather than pitch cues. It was suggested that the right hemisphere is superior to the left in processing stimuli that are \"non-temporal.\"
\r\n\r\nMusical expression was investigated in patients who had transiently lost the function of one hemisphere following intracarotid amytal injection. It was observed that after right hemisphere depression, singing was devoid of pitch at a time when speech was only minimally disturbed.\r\nConversely, singing was much less affected than speech after left hemisphere depression. This differential effect of amytal depression is supportive of the idea that the right hemisphere is used for pitch control in singing whereas the left hemisphere is used expressly for speech.
\r\n\r\nSinging was also studied in two young patients with surgical hemispherectomies for non-infantile causes. One patient who had a right hemisphere removal with no evidence of aphasia, sang most songs poorly. He also failed pitch discrimination tests wherein he could not distinguish two tones that were separated by an interval of less than one musical step. Another patient with a left hemispherectomy produced the opposite results. She had great difficulties in expressive speech yet could sing with excellent pitch control and intonation. These cases support the previous conclusion that the right hemisphere is necessary for correct pitch production in singing.
\r\n\r\nDichotic listening studies on patients with complete surgical division of the corpus callosum indicated that the right hemisphere also had some capacity to understand and manually express verbs and verbal commands. This was evidenced in instances where only the command presented to the left ear was manually performed at a time when another command presented simultaneously to the right ear was the only one that was verbally reported. The indication is that the right hemisphere understood and performed the required action when the left hemisphere was apparently unaware. However, it was also shown that for most dichotic verbal tests the left hemisphere still has dominant control over the right.
\r\n\r\nDichotic listening studies also indicated that the left hemisphere could separately monitor stimuli in the ipsilateral along with stimuli in the contralateral pathway. This was contradictory to previous conclusions that the contralateral pathway suppresses the ipsilateral in dichotic competition. Response time studies carried out in these callosum-sectioned patients investigated organization of the two cortical\r\nsystems that separately analyzed stimuli from the two ascending paths.
\r\n\r\nIt was found that response times for repeating words to the right ear were faster than for words in the left ear. Control tests showed the cause of this difference was not in delay of transmission in ascending routes, nor in differences of perception in the two systems.\r\nIt was deduced .that the cause was an asymmetrical process of memory retrieval for translation into motor impulses to the speech apparatus.
\r\n", "doi": "10.7907/MPJG-WA43", "publication_date": "1973", "thesis_type": "phd", "thesis_year": "1973" }, { "id": "thesis:11184", "collection": "thesis", "collection_id": "11184", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09172018-103619092", "primary_object_url": { "basename": "Segal_M_1973.pdf", "content": "final", "filesize": 63901754, "license": "other", "mime_type": "application/pdf", "url": "/11184/1/Segal_M_1973.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "The Hippocampus as a Learning Machine", "author": [ { "family_name": "Segal", "given_name": "Menahem", "clpid": "Segal-Menahem" } ], "thesis_advisor": [ { "family_name": "Olds", "given_name": "James", "clpid": "Olds-J" } ], "thesis_committee": [ { "family_name": "Olds", "given_name": "James", "clpid": "Olds-J" }, { "family_name": "Bonner", "given_name": "James Frederick", "clpid": "Bonner-J-F" }, { "family_name": "Fender", "given_name": "Derek H.", "clpid": "Fender-D-H" }, { "family_name": "Sperry", "given_name": "Roger Wolcott", "clpid": "Sperry-R-W" }, { "family_name": "Strumwasser", "given_name": "Felix", "clpid": "Strumwasser-F" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "A series of experiments were conducted with the purposes of\r\ndescribing a functional pathway in the rat hippocampus, characterizing some conditions necessary for activating it, and identifying critical steps in this pathway. In all experiments a classical conditioning paradigm was used and the responses of units in the hippocampus and related forebrain structures to the conditioned stimulus were measured. In the first experiment a few differences between dentate, CA-3, and CA-1, the main fields of the hippocampus, were found. Units in the dentate were first to acquire a conditioned response, CA-3 followed and CA-1 was last. This order fits with the anatomical pathway. However, dentate responses were phasic, that is, did not outlast the CS-US interval, and were not specific to the conditioned stimulus. The responses of CA-3 and CA-1 units, on the other hand, were sustained and specific. The second experiment was devoted to the analysis of conditioned response latencies, in the hippocampus\r\nas well as in septum, subiculum, cingulate, entorhinal, and related structures, all known to be input stages to the hippocampus. In this experiment unconditioned short response latencies were found in the medial septum, one of the afferents of the hippocampus. These were not changed in the process of learning. The shortest conditioned response latencies were found in area CA-3 of the hippocampus. Units in area CA-1 followed, but units in dentate did not precede those of CA-3. Units in entorhinal cortex, the other main afferent to the hippocampus did not seem to precede hippocampal units either. The special relations between the hippocampus and the dentate were demonstrated in another part of this experiment, where dentate units lost their conditioned responses, in the process of extinction, before those of CA-3 and CA-1. It was postulated that septal input triggers CA-3 responses and these\r\nwould be maintained in the presence of reinforcing dentate and\r\nentorhinal inputs.
\r\n\r\nThe relations between the dentate and the hippocampus were\r\nfurther studied in two experiments in which aversive electric shock served as an unconditioned stimulus. In experiment 3 food and shock served as unconditioned stimuli on alternate days. In\r\nexperiment 4 food and shock were presented in the same sessions as unconditioned stimuli to two different CS's. Dentate units had an excitatory conditioned response to a food signal and an inhibitory conditioned response to a shock signal in both experiments. Hippocampal units had excitatory responses to both signals. Acquisition of a conditioned response was not demonstrated within the hippocampus when the conditioned stimulus preceded shock and was slow when food or shock were applied following two different signals in the same session. However, when first trained that a signal precedes food, the conditioned response would be maintained in the hippocampus even if shock is now the US. The dentate is probably involved in the initiation of a conditioned response in the hippocampus but not in the maintenance of it.
\r\n\r\nA sensory-sensory paradigm (experiment 5) has demonstrated\r\nthe presence of unconditioned unhabituated sensory responses in two of the afferents to the hippocampus, that is, the medial septum and the cingulate cortex. It failed to show signs of conditioning in the hippocampus proper. It was proposed that in the absence of an appetitive reward and the activity of the entorhinal-dentate pathway, conditioned responses in hippocampus cannot be established.
\r\n\r\nConditioned entorhinal responses (experiment 6) had long\r\nlatency but also long time constant. Their evoked activity was\r\nmaintained for periods as long as one minute. It was found that\r\nhippocampal responses were larger, if the conditioned stimulus was applied within one minute from the previous trial. Hence, a\r\ncorrelation between hippocampal responses and entorhinal firing\r\nrate was demonstrated. On the basis of these experiments it was\r\nproposed that septal input enters the hippocampus at the CA-3\r\narea, is able to selectively activate these cells only in the\r\npresence of facilitation produced by entorhinal and dentate activity. The facilitatory entorhinal activity is triggered mainly by positive reward.
\r\n", "doi": "10.7907/P1SD-Z263", "publication_date": "1973", "thesis_type": "phd", "thesis_year": "1973" }, { "id": "thesis:9694", "collection": "thesis", "collection_id": "9694", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05022016-093643296", "primary_object_url": { "basename": "Kornblith_cl_1972.pdf", "content": "final", "filesize": 21562260, "license": "other", "mime_type": "application/pdf", "url": "/9694/1/Kornblith_cl_1972.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Conditioned Responses in the Reticular Formation", "author": [ { "family_name": "Kornblith", "given_name": "Carol Lee", "clpid": "Kornblith-Carol-Lee" } ], "thesis_advisor": [ { "family_name": "Olds", "given_name": "James", "clpid": "Olds-J" } ], "thesis_committee": [ { "family_name": "Olds", "given_name": "James", "clpid": "Olds-J" }, { "family_name": "Owen", "given_name": "Ray David", "clpid": "Owen-R-D" }, { "family_name": "Strumwasser", "given_name": "Felix", "clpid": "Strumwasser-F" }, { "family_name": "Van Harreveld", "given_name": "Anthonie", "clpid": "Van-Harreveld-A" }, { "family_name": "Wiersma", "given_name": "Cornelis A. G.", "clpid": "Wiersma-C-A-G" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "Unit activity was recorded from the midbrain and pons of 40 freely moving rats in an appetitive classical conditioning situation. Responses to auditory stimuli were observed from 100 units before and during a conditioning procedure in which presentation of food occurred 1 sec after the onset of the auditory stimulus. Conditioned unit responses (i.e., spike rate accelerations or decelerations) were considered to be positive when 1) no similar responses appeared prior to conditioning, and 2) latencies were equal to or less than those of sensory responses derived from the inferior colliculus. Such short latency conditioned unit responses were recorded from 11 probes located in the mid-lateral pert of the ventral region of the brain stem. This region was differentiated from paramedian, far lateral and dorsal parts of the brain stem reticular formation. Conditioned unit responses of considerably longer latencies were recorded from 76 probe located in these other regions. Among the longer latency responses interesting differences appeared in experiments conducted after the first conditioning series was completed. With additional training, units in the \"reticular activating system\" of midbrain and pons tended to yield stabilized responses in the early portion of the\r\nCS-US interval closely related in time to the orientation responses evoked by the CS. In contrast, the responses of units in the limbic midbrain tended to stabilize in the later part of the CS-US interval closely related in time to preparatory responses tied to the US. During extinction when the auditory stimulus was no longer followed by presentation of food, many of the responses were reduced to their pre-conditioning levels. However, there was a tendency for units which had displayed short latency responses on the first conditioning day to be more resistant to extinction than units which had displayed longer latency conditioned responses. The data were interpreted as indicating a local correlate of learning in the reticular formation of midbrain end pons and a separation of the midbrain system into at least two areas: 1) the classical \"reticular activating system\" related to orienting reactions, and 2) the limbic midbrain areas related to drives and rewards. Because the ventral and mid-lateral area with very short latency conditioned responses was not clearly tied to either of these; it was considered as possibly representing a third division.", "doi": "10.7907/J6N6-EV96", "publication_date": "1972", "thesis_type": "phd", "thesis_year": "1972" } ]