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Open Access Publications from the University of California

Scholarly Works (10 results)

  • Article
  • Peer Reviewed
International Journal of Comparative Psychology, Volume 7, Issue 1 (1994)

Minnow predation by 10 young American alligators (Alligator mississippiensis)was systematically measured during four daily time periods under four different conditions of lighting in order to investigate a circadian rhythm of redatory behavior.The four daily time periods were night (1:00 a.m. -7.00  a.m.),morning (7.00 a.m.- 1:00 p.m.), afternoon (1:00 p.m.-7:00 p.m.), and evening (7:00p.m. -1:00 a.m.). Each of the following lighting conditions had a duration of 4 weeks:continuous complete darkness (DD); continuous artificial illumination (LL); naturally varying Ught-dark conditions (natural LD); and reversed light-dark conditions with artificial lights on at sunset and off at sunrise (reversed LD). Predatory behavior (i.e., the number of prey fish consumed wholly or partially during each test session) varied significantly as a function of the interaction between time period and lighting condition.Under natural LD, the mean number of prey killed during  night sessions was significantly higher than either morning or afternoon sessions. Under reversed LD,the pattern of predation reversed from that exhibited under normal Ughting, with both morning and afternoon predation significantly higher than either evening or night. Under conditions of continuous illumination (LL and DD) the natural LD circadian pattern persisted for over 1 week with significantly higher predation rates during the night periods as ompared to the morning and afternoon periods. The gradual transition of predation pattern in response to manipulations of the light-dark cycle suggests that the circadian rhythm of alligator predadon is dependent upon light-dark variation for entrainment.

    Cover page: Light meditation of Circadian Predatory Behavior in the Young AlligatorCreative Commons 'BY' version 4.0 license
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2024)
    Context contributes to multiple aspects of human episodic memory including segmentation and retrieval. The present studies tested if, in adult male and female mice, context influences the encoding of odors encountered in a single unsupervised sampling session of the type used for the routine acquisition of episodic memories. The three paradigms used differed in complexity (single vs. multiple odor cues) and period from sampling to testing. Results show that males consistently encode odors in a context-dependent manner: the mice discriminated novel from previously sampled cues when tested in the chamber of initial cue sampling but not in a distinct yet familiar chamber. This was independent of the interval between cue encounters or the latency from initial sampling to testing. In contrast, female mice acquired both single cues and the elements of multi-cue episodes, but recall of that information was dependent upon the surrounding context only when the cues were presented serially. These results extend the list of episodic memory features expressed by rodents and also introduce a striking and unexpected sex difference in context effects.
      Cover page: Sex differences in the context dependency of episodic memory.
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2007)

      Stabilization of long-term potentiation (LTP) depends on multiple signaling cascades linked to actin polymerization. We used one of these, involving phosphorylation of the regulatory protein cofilin, as a marker to test whether LTP-related changes occur in hippocampal synapses during unsupervised learning. Well handled rats were allowed to explore a compartmentalized environment for 30 min after an injection of vehicle or the NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). Another group of rats consisted of vehicle-injected, home-cage controls. Vehicle-treated rats that explored the environment had 30% more spines with dense phosphorylated (p) cofilin immunoreactivity in hippocampal field CA1 than did rats in the home-cage group. The increase in pCofilin-positive spines and behavioral evidence for memory of the explored environment were both eliminated by CPP. Coimmunostaining for pCofilin and the postsynaptic density protein 95 (PSD-95) showed that synapses on pCofilin-positive spines were substantially larger than those on neighboring (pCofilin-negative) spines. These results establish that uncommon cellular events associated with LTP, including changes in synapse size, occur in individual spines during learning, and provide a technique for mapping potential engrams.

        Cover page: Evidence that long-term potentiation occurs within individual hippocampal synapses during learning.
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2017)
        Humans routinely use past experience with complexity to deal with novel, challenging circumstances. This fundamental aspect of real-world behavior has received surprisingly little attention in animal studies, and the underlying brain mechanisms are unknown. The present experiments tested for transfer from past experience in rats and then used quantitative imaging to localize synaptic modifications in hippocampus. Six daily exposures to an enriched environment (EE) caused a marked enhancement of short- and long-term memory encoded during a 30-min session in a different and complex environment relative to rats given extensive handling or access to running wheels. Relatedly, the EE animals investigated the novel environment in a different manner than the other groups, suggesting transfer of exploration strategies acquired in earlier interactions with complexity. This effect was not associated with changes in the number or size of excitatory synapses in hippocampus. Maps of synapses expressing a marker for long-term potentiation indicated that encoding in the EE group, relative to control animals, was concentrated in hippocampal field CA1. Importantly, <1% of the total population of synapses was involved in production of the regional map. These results constitute the first evidence that the transfer of experience profoundly affects the manner in which hippocampus encodes complex information.
          Cover page: Experiential learning in rodents: past experience enables rapid learning and localized encoding in hippocampus
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2018)
          Endocannabinoids (ECBs) depress transmitter release at sites throughout the brain. Here, we describe another form of ECB signaling that triggers a novel form of long-term potentiation (LTP) localized to the lateral perforant path (LPP) which conveys semantic information from cortex to hippocampus. Two cannabinoid CB1 receptor (CB1R) signaling cascades were identified in hippocampus. The first is pregnenolone sensitive, targets vesicular protein Munc18-1 and depresses transmitter release; this cascade is engaged by CB1Rs in Schaffer-Commissural afferents to CA1 but not in the LPP, and it does not contribute to LTP. The second cascade is pregnenolone insensitive and LPP specific; it entails co-operative CB1R/β1-integrin signaling to effect synaptic potentiation via stable enhancement of transmitter release. The latter cascade is engaged during LPP-dependent learning. These results link atypical ECB signaling to the encoding of a fundamental component of episodic memory and suggest a novel route whereby endogenous and exogenous cannabinoids affect cognition.
            Cover page: Atypical Endocannabinoid Signaling Initiates a New Form of Memory-Related Plasticity at a Cortical Input to Hippocampus.
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2014)
            Recent work showed that unsupervised learning of a complex environment activates synaptic proteins essential for the stabilization of long-term potentiation (LTP). The present study used automated methods to construct maps of excitatory synapses associated with high concentrations of one of these LTP-related proteins [CaMKII phosphorylated at T286/287, (pCaMKII)]. Labeling patterns across 42 sampling zones covering entire cross sections through rostral hippocampus were assessed for two groups of rats that explored a novel two-room arena for 30 min, with or without a response contingency involving mildly aversive cues. The number of pCaMKII-immunopositive (+) synapses was highly correlated between the two groups for the 21 sampling zones covering the dentate gyrus, CA3c/hilus, and apical dendrites of field CA1, but not for the remainder of the cross section. The distribution of pCaMKII+ synapses in the large uncorrelated segment differed markedly between the groups. Subtracting home-cage values removed high scores (i.e., sampling zones with a high percentage of pCaMKII+ contacts) in the negative contingency group, but not in the free-exploration animals. Three sites in the latter had values that were markedly elevated above other fields. These mapping results suggest that encoding of a form of memory that is dependent upon rostral hippocampus reliably occurs at high levels in discrete anatomical zones, and that this regionally differentiated response is blocked when animals are inhibited from freely exploring the environment by the introduction of a mildly aversive stimulus.
              Cover page: A Map of LTP-Related Synaptic Changes in Dorsal Hippocampus Following Unsupervised Learning
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2014)
              Recent work showed that unsupervised learning of a complex environment activates synaptic proteins essential for the stabilization of long-term potentiation (LTP). The present study used automated methods to construct maps of excitatory synapses associated with high concentrations of one of these LTP-related proteins [CaMKII phosphorylated at T286/287, (pCaMKII)]. Labeling patterns across 42 sampling zones covering entire cross sections through rostral hippocampus were assessed for two groups of rats that explored a novel two-room arena for 30 min, with or without a response contingency involving mildly aversive cues. The number of pCaMKII-immunopositive (+) synapses was highly correlated between the two groups for the 21 sampling zones covering the dentate gyrus, CA3c/hilus, and apical dendrites of field CA1, but not for the remainder of the cross section. The distribution of pCaMKII+ synapses in the large uncorrelated segment differed markedly between the groups. Subtracting home-cage values removed high scores (i.e., sampling zones with a high percentage of pCaMKII+ contacts) in the negative contingency group, but not in the free-exploration animals. Three sites in the latter had values that were markedly elevated above other fields. These mapping results suggest that encoding of a form of memory that is dependent upon rostral hippocampus reliably occurs at high levels in discrete anatomical zones, and that this regionally differentiated response is blocked when animals are inhibited from freely exploring the environment by the introduction of a mildly aversive stimulus.
                Cover page: A Map of LTP-Related Synaptic Changes in Dorsal Hippocampus Following Unsupervised LearningCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2016)
                Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior.

                Significance statement

                Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be mostly reversed by long-term, oral administration of a positive allosteric modulator of AMPA-type glutamate receptors. Dendritic recovery was accompanied by improvements to both synaptic plasticity and the encoding of long-term memory of a novel, complex environment. Because the short half-life compound had no evident negative effects, the results suggest a plausible strategy for treating age-related neuronal deterioration.
                  Cover page: Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged RatsCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2014)
                  Recent work showed that unsupervised learning of a complex environment activates synaptic proteins essential for the stabilization of long-term potentiation (LTP). The present study used automated methods to construct maps of excitatory synapses associated with high concentrations of one of these LTP-related proteins [CaMKII phosphorylated at T286/287, (pCaMKII)]. Labeling patterns across 42 sampling zones covering entire cross sections through rostral hippocampus were assessed for two groups of rats that explored a novel two-room arena for 30 min, with or without a response contingency involving mildly aversive cues. The number of pCaMKII-immunopositive (+) synapses was highly correlated between the two groups for the 21 sampling zones covering the dentate gyrus, CA3c/hilus, and apical dendrites of field CA1, but not for the remainder of the cross section. The distribution of pCaMKII+ synapses in the large uncorrelated segment differed markedly between the groups. Subtracting home-cage values removed high scores (i.e., sampling zones with a high percentage of pCaMKII+ contacts) in the negative contingency group, but not in the free-exploration animals. Three sites in the latter had values that were markedly elevated above other fields. These mapping results suggest that encoding of a form of memory that is dependent upon rostral hippocampus reliably occurs at high levels in discrete anatomical zones, and that this regionally differentiated response is blocked when animals are inhibited from freely exploring the environment by the introduction of a mildly aversive stimulus.
                    Cover page: A Map of LTP-Related Synaptic Changes in Dorsal Hippocampus Following Unsupervised Learning
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2016)
                    The endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), a key modulator of synaptic transmission in mammalian brain, is produced in dendritic spines and then crosses the synaptic junction to depress neurotransmitter release. Here we report that 2-AG-dependent retrograde signaling also mediates an enduring enhancement of glutamate release, as assessed with independent tests, in the lateral perforant path (LPP), one of two cortical inputs to the granule cells of the dentate gyrus. Induction of this form of long-term potentiation (LTP) involved two types of glutamate receptors, changes in postsynaptic calcium, and the postsynaptic enzyme that synthesizes 2-AG. Stochastic optical reconstruction microscopy confirmed that CB1 cannabinoid receptors are localized presynaptically to LPP terminals, while the inhibition or knockout of the receptors eliminated LPP-LTP. Suppressing the enzyme that degrades 2-AG dramatically enhanced LPP potentiation, while overexpressing it produced the opposite effect. Priming with a CB1 agonist markedly reduced the threshold for LTP. Latrunculin A, which prevents actin polymerization, blocked LPP-LTP when applied extracellularly but had no effect when infused postsynaptically into granule cells, indicating that critical actin remodeling resides in the presynaptic compartment. Importantly, there was no evidence for the LPP form of potentiation in the Schaffer-commissural innervation of field CA1 or in the medial perforant path. Peripheral injections of compounds that block or enhance LPP-LTP had corresponding effects on the formation of long-term memory for cues conveyed to the dentate gyrus by the LPP. Together, these results indicate that the encoding of information carried by a principal hippocampal afferent involves an unusual, regionally differentiated form of plasticity.
                      Cover page: A Primary Cortical Input to Hippocampus Expresses a Pathway-Specific and Endocannabinoid-Dependent Form of Long-Term Potentiation
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