A time course analysis of stem cell activity following brain injury in food-storing black-capped chickadees (poecile atricapillus).
Gardner, R. D. (2010)
Thesis Presented to California State University, Long Beach.
Compared to non-storing juncos, cell proliferation is enhanced in chickadees. Following hippocampal injury, however, the chickadee hippocampus has fewer new cells than juncos, possibly due to rates of cellular turnover. To examine the temporal characteristics of cell birth in fall-caught Maine chickadees, all birds received a unilateral hippocampal lesion and one injection of BrdU (mitotic label) immediately or 24 hours post-lesion. Chickadees were euthanized 2 or 168 hours post-BrdU, after which BrdU-IR cells were counted in the hippocampus and adjacent stem cell rich pSVZ. Surprisingly, the pSVZ showed no injury-induced increase in cell birth at any time. Injury-induced hippocampal cell proliferation, however, was observed 24 or more hours post-lesion. Over time, BrdU-IR cell density in both structures remained relatively constant. Therefore, speed of cellular turnover fails to explain the differences between chickadees and juncos. Additionally, the stem cell layer does not upregulate cell birth following injury, as in other species.
Species-specific injury-induced cell proliferation in the hippocampus and subventricular zone of food-storing and nonstoring wild birds.
Law, L. M., Gardner, R. D., Allen, T. A., & Lee, D. W. (2010)
Developmental Neurobiology 70(1), 16-27, doi: 10.1002/dneu.20748
Cells are continuously born and incorporated into the adult hippocampus (HP). Adult neurogenesis might act to increase the total number of cells or replace dead cells. Thus, neurogenesis might be a primary factor in augmenting, maintaining, or even recovering functions. In zebra finches, HP injury increases cell proliferation in the HP and stem cell rich subventricular zone (SVZ). It is unknown what effect injury has on a species dependent upon the HP for survival in the wild. In food-storing birds, recovery of caches is seasonal, necessary for survival, dependent upon the HP and is concomitant with a peak in HP neurogenesis. During the fall, food-storing black-capped chickadees (BCCs) and nonstoring dark-eyed juncos (DEJs) were captured and given a unilateral penetrating lesion to the HP one day later. On day 3, birds were injected with the mitotic marker 5-bromo-2'-deoxyuridine (BrdU) and perfused on day 10. If unlesioned, more BrdU-labeled cells were observed in the HP and SVZ of BCCs compared to DEJs, indicating higher innate cell proliferation or incorporation in BCCs. If lesioned, BrdU-labeled cells increased in the injured HP of both species; however, lesions caused larger increases in DEJs. DEJs also showed increases in BrdU-labeled cells in the SVZ and contralateral HP. BCCs showed no such increases on day 10. Thus, during the fall food-storing season, storers showed suppressed injury-induced cell proliferation and/or reduced survival rates of these new cells compared to nonstorers. These species differences may provide a useful model for isolating factors involved in cellular responses following injury.
Standardized Beck Depression Inventory-II Scores for Male Veterans Coping With Chronic Pain.
Lopez, M.N., Pierce, R. S., Gardner, R. D., & Hanson, R.W. (2012). Psychological Services 10(2), 257-263, doi: 10.1037/a0027920
The Beck Depression Inventory II (BDI-II) has been suspected of overestimating the level of depression in individuals that endure chronic pain. Using a sample (N = 345) of male military veterans with chronic pain enrolled in an outpatient treatment program, a factor analysis on the BDI-II revealed a "Somatic Complaints" factor along with 2 other factors we labeled "Negative Rumination" and "Mood." Standardized scores were provided for each BDI-II factor score, Total score, and Total minus Somatic score. The internal consistency reliabilities (Gilmer-Feldt and alpha coefficients) for all scores were found to be clinically acceptable. Item-Total score correlations found that all of the BDI-II items were good discriminators (r > .30). We conclude that the normative data provided should help control for somatic responding by male chronic pain veterans on the BDI-II. We highly recommend that clinicians and researchers use the norm-referenced method when interpreting BDI-II scores from individuals suffering from chronic pain.
The modularity debate in evolutionary psychology: A response to Barrett and Kurzban (2006).
Chiappe, D., & Gardner, R. D. (2012). Theory & Psychology, 22(5), 669-682, doi.org/10.1177/0959354311398703
The adherence of evolutionary psychology (EP) to the massive modularity thesis has generated considerable controversy. Barrett and Kurzban argue that much of the debate is misplaced because critics have incorrectly characterized the sense of modularity involved in EP. They offer an account centered on “functional specialization,” an emphasis on formal properties of representations, and an eschewing of references to content domains. We argue that their concept of modularity is at odds with the claims made by EP advocates. Indeed, their definition of modularity is so broad that it includes mechanisms traditionally rejected by EP. Furthermore, their concept of modularity has limited usefulness in explaining the existence of mechanisms designed to deal with novel challenges and with the development of novel solutions to longstanding adaptive problems. A model based on Potts’ concept of “variability selection” is offered as an explanation of such mechanisms.
Neuroscience Abstracts, Posters, & Professional Lectures
Cell Proliferation in the Septo-Hippocampal Pathway: Season, Lesion, and Species Effects.
Gardner, R. D. (2009).
Colloquium presented at Bowdoin College on October 1st, 2009 for the Departments of Neuroscience and Psychology in Brunswick, ME.
Adult Neurogenesis in the Hippocampus and Septum of Food-Storing Birds
Gardner, R. D. (2009).
Guest lecture presented at Bowdoin College on October 22nd, 2009 for a Seminar in Neuroscience for the Departments of Neuroscience and Psychology in Brunswick, ME.
Lesion-induced neurogenesis: A comparison between neurogenic and non-neurogenic brain regions.
Drumheller, K. M., Battistoni, B., Chapleau, J., Chinn, E., Gardner, R., Latimore, A. D., Mana, A., McCulloch, K., Minakata, K., Tieu, R., Law, L. M., & Lee, D. W. (2007). 3rd place award winner at California State University, Long Beach during Psi-Chi student research poster fair.
Adult neurogenesis (the birth of new neurons derived from adult stem cells) holds the possibility of contributing to structural and functional recovery following brain damage. Adult neurogenesis occurs naturally in vertebrate animals in limited brain regions (e.g., the hippocampus). Injury-induced neurogenesis, however, has been shown to occur in additional brain regions that are normally non-neurogenic (e.g., the avian hypothalamus, and mammalian neocortex). Lesion-induced neurogenesis has yet to be investigated in both neurogenic and non-neurogenic regions in the same study. This study will directly compare the effects of injury to neurogenic and non-neurogenic regions of an adult song bird. Experimenters will bilaterally lesion groups of male zebra finches in one of three locations: the hippocampus (HP; neurogenic), the higher vocal center (HVC; neurogenic), and the hyperstriatum accessorium (HA; non-neurogenic). Utilizing BrdU as a marker of cell proliferation, we will count all BrdU-positive cells in the injured regions. By comparing these groups to an unlesioned control group, it is expected that all three regions will demonstrate some lesion-induced neurogenesis; however, because the HP and HVC are inherently neurogenic, significantly more neurogenesis is expected to occur in these locations. Such results could contribute to a clearer understanding of the purpose of these new adult cells and would hold important implications for future treatment options following brain damage.
Injury-Induced Loss and Recovery of Function in Male Zebra Finch: The Effects of Lesion on Song, Grooming, and Aggression.
Latimore, A. D. , Battistoni, B., Chapleau, J., Chinn, E., Drumheller, K. M., Gardner, R.D., Mana, A., McCulloch, K., Minakata, K., Tieu, R., Law, L. M., Lee, D. W. (2007). Poster presented at California State University, Long Beach during Psi-Chi student research poster fair.
Previous research on targeted neuronal cell death has shown that lesioning the higher vocal center (HVC) severely impairs song production in male zebra finches, with some recovery of function over time. However, it is not known if other mating behaviors such as aggression and/or grooming are affected. The current study proposes to lesion the HVC in an attempt to determine whether song is the only mating behavior lost and whether it will recover in a time-dependent way. While the HVC is the major region of interest, a number of other sites will be lesioned as surgical controls, including the hippocampus (HP) and the hyperstriatum accessorium (HA). In doing so, we hope to chronologue the process of functional recovery, note environmental correlates, and compare the effects of HVC and non-HVC lesions on mating-related behaviors.
Seventy male zebra finches, paired in same-sex cages will be acclimated to their surroundings. They will be videotaped during exposure to female birds in separate cages to obtain baseline measures of singing, grooming, and male-to-male aggression -- all potential behaviors in the mating system repertoire. Birds will then receive either an HVC, HP, HA, or sham lesion. Post-lesion observational data will be collected prior to perfusion as well.
We hypothesize that only HVC lesions will impair song production. In addition, with time, we expect to observe some functional recovery of song as well. The results of this study will allow for a more thorough understanding of the effects of brain injury on loss and recovery of function.
Sex Differences in Cell Proliferation Following Estrogen Depletion in the Adult Zebra Finch.
Gardner, R.D, & Lee, D. W. (2008). Poster presented at California State University, Long Beach during Psi-Chi student research poster fair.
Estrogens influence neuron proliferation and survival. Following hippocampal injury in female zebra finches, aromatase (estrogen synthase) is upregulated, possibly creating a locally synthesized, estrogen-rich, microenvironment conducive to cell proliferation and brain repair. The aromatase inhibitor fadrozole suppresses proliferation in the female hippocampus and stem cell-rich subventricular zone (SVZ). Comparatively, males have more hippocampal aromatase and injury-induced cell birth following a hippocampal lesion. This robust injury response may be due to their higher levels of aromatase and/or its estrogen products.
The proposed study will investigate sex differences in cell proliferation following estrogen depletion. Male and female zebra finches will be fed fadrozole or saline daily for 18 days. Birds will receive no lesion, or a unilateral lesion to the right hippocampus on Day 16; an injection of the mitotic marker BrdU on Day 17; and perfusion on Day 18. BrdU/NeuN immunohistochemistry will be employed to visualize new cells in the hippocampus and SVZ, and to determine cell phenotype.
Supporting previous research, unlesioned males and females should have equal rates of cell proliferation. Fadrozole is expected to suppress cell proliferation in both sexes, regardless of lesion. Thus, fadrozole-fed birds should have significantly fewer new cells than saline-fed birds. If males show more injury-induced cell proliferation due to higher levels of hippocampal aromatase, administration of fadrozole should eliminate that sex difference. Examination of sex differences in response to brain injury holds profound implications for designing estrogen-based therapies to minimize loss of function due to injury or disease, and facilitate recovery.
Evidence for Evolved Adaptive Specialization in the Food-Storing Black-Capped Chickadee (Poecile atricapillus).
Gardner, R. D., Mitterling, K. L., Law, L. M., Ramus, S. J., & Lee, D. W. (2008). Poster presented at California State University, Long Beach during Psi-Chi student research poster fair.
Food-storing birds show extraordinary ability to remember numerous cache locations over many hours and even months. Successful retrieval of caches relies on hippocampus-dependent spatial memory. The hippocampus, in turn, shares reciprocal connections with the septum, a structure also involved with memory. The survival value of hippocampal-dependent recall for cache locations may have created an evolved brain specialization in food-storers. In support, food-storing birds have a larger hippocampus and septum than non-storers, especially during the fall when food-storing commences. Others report, that the hippocampus is larger during the spring, not fall. The current study sought to resolve these discrepancies by comparing volumes and cell proliferation in the hippocampus and septum of food-storing black-capped chickadees (Poecile atricapillus; BCC) and non-storing dark-eyed juncos (Junco hyemalis; DEJ) during the fall and spring in coastal Maine. All birds were injected once with the mitotic marker BrdU 48 hours after collection; cell proliferation was expressed as density of BrdU-immunoreactive cells per unit area (cells per mm2).
Results confirmed that the hippocampus and septum of BCCs were significantly larger, and had more BrdU-IR cells. However, both species demonstrated an increase in volumes of both hippocampus and septum during the spring, not fall. While DEJs showed no significant seasonal changes in cell proliferation, a fall increase in BrdU-IR cells in the hippocampus and septum were observed in BCCs. Results indicated that cell proliferation may be a selective adaptation related to food-storing behavior; a mechanism other than proliferation may cause spring volumetric increases.
Species-specific injury-induced cell proliferation in the hippocampus and subventricular zone of food-storing and non-storing wild birds.
Gardner, R. D., Law, L. M., Drumheller, K. M., Allen, T. A., & Lee, D. W. (2009). Poster presented at the All University Celebration of Research at California State University Long Beach.
List Body
Seasonal Differences in Cell Proliferation in the Hippocampus and Septum of Food-Storing and Non-Storing Birds.
2008). Research presented at the All University Celebration of Research at California State University Long Beach.
Cell Incorporation in the Septo-Hippocampal Pathway of Food-storing and Non-storing Birds: Season, Lesion, and Species Effects.
Gardner, R. D., Law, M. L., Mitterling, K. L., Ramus, S. J., & Lee, D. W. (2008). Poster presented at the Scatter Hoarding Conference at Cornell University, Ithaca, NY.
The hippocampus and septum are involved in memory formation and share reciprocal connections. Following hippocampal lesions, all birds studied thus far show injury-induced hippocampal cell proliferation and incorporation; however, the septum has not been evaluated. Food-storing black-capped chickadees and non-storing dark-eyed juncos were collected in coastal Maine. One day post-capture, fall birds (October, November) received a penetrating lesion to the right hippocampus or no lesion; spring birds (April, May) received no lesion. All were injected with the mitotic marker BrdU on day 2, then perfused on day 10. Results confirmed larger hippocampal and septal volumes in chickadees compared to juncos, regardless of season. Both species showed volumetric increases in both regions during the spring, not fall, therefore volumetric increases may not be tightly associated with food-storing, or specific collection month is a critically important factor. BrdU-IR cells were observed in both regions, species, and seasons. Fall chickadees had higher BrdU-IR hippocampal cell densities than all others, indicating that hippocampal cell incorporation is enhanced in storers, especially during the fall. In the septum, there were no significant density differences between species. While season did not affect junco septum densities, fall chickadees had significantly higher BrdU-IR cell densities than spring chickadees indicating that the septum may also be involved in food-storing. Following hippocampal lesioning, only juncos showed increases in BrdU-IR septum cell densities. Since the hippocampus and septum share reciprocal projections, damage to one induces changes in both, but only in non-storers indicating that spread of injury may be restricted in storers.
Cell Proliferation in the Septo-Hippocampal Pathway: Season, Lesion, and Species Effects.
Gardner, R. D., Law, L. M., Mitterling, K. L., Ramus, S. J., & Lee, D.W. (2008). Society for Neuroscience Abstracts
Adult neurogenesis occurs in the avian hippocampus; in food-storing birds, it may play a role in their extraordinary ability to remember numerous cache locations. Successful retrieval of caches relies on hippocampal-dependent spatial memory. The hippocampus, in turn, shares reciprocal connections with the septum, a structure also involved with memory. Previous research has demonstrated that food-storing birds have larger hippocampal and septal volumes as well as more hippocampal neurogenesis compared to non-storers. Following hippocampal lesions, all birds studied thus far show injury-induced cell proliferation in the hippocampus. Newly born cells in the septum have not been evaluated. The current study examined cell proliferation in the septum of food storing black-capped chickadees (BCC) and non-storing dark-eyed juncos (DEJ) collected in coastal Maine (1) during the spring and fall and (2) following a unilateral hippocampal lesion during the fall. On the day following capture, birds received either a unilateral penetrating lesion to the right hippocampus or no lesion; two days following capture all were injected once with the mitotic marker BrdU. Cell proliferation was expressed as the density of BrdU-immunoreactive (BrdU-IR) cells per unit area of the septum (cells per mm2). BrdU-IR cells were observed in the septum of both BCCs and DEJs, during both spring and fall; there were no significant differences between the species in either season. However, fall-caught BCCs, but not DEJs, had significantly more BrdU-IR cells in the septum than those caught in the spring indicating that this may be implicated in their fall increase in food-storing. Unlike DEJs, as a result of a hippocampal lesion, BCCs failed to show injury-induced septal cell birth. This pattern is not observed in either the non-storing DEJ, or zebra finch (in previous studies). BCCs do show injury-induced hippocampal cell birth but to a significantly lower extent than DEJs. However, only DEJs (and zebra finch) show hippocampal injury-induced cell proliferation in the hippocampus, as well as the stem cell rich subventricular zone (SVZ) adjacent to the hippocampus, and septum. Therefore combined with previous research, this septum evidence strongly indicates that following a hippocampal injury, food-storing BCCs may inhibit, or are simply incapable of further increases in cell birth during the fall.
Injury induced cell proliferation and incorporation: Comparing a food-storing and non-storing species.
Law, M. L., Gardner, R. D., Drumheller, K. M., & Lee, D. W. (2008). Poster presented at the Scatter Hoarding Conference at Cornell University, Ithaca, NY.
Adult neurogenesis has been observed in response to season, learning, experience, and injury. Food-storing birds show a peak in hippocampal neurogenesis during the fall concomitant with a peak in food storing, a hippocampus-dependent activity. In zebra finch, the hippocampus and adjacent stem cell rich subventricular zone (SVZ) respond to injury with an increase in cell proliferation and incorporation. Since food-storing birds undergo seasonal neurogenesis, this study evaluated the response following hippocampal injury specifically during the fall storing season. Nine black-capped chickadees and dark-eyed juncos were collected in coastal Maine during autumn, 2005. Birds received a single penetrating lesion to the right hippocampus, an injection of the mitotic marker BrdU 24 hours post-lesion, and were then perfused 7 days post-BrdU. The density of BrdU-IR cells were calculated for the hippocampus, proximal SVZ (pSVZ, adjacent to the hippocampus), and distal SVZ (dSVZ, nonadjacent). Unlesioned chickadees had higher BrdU-IR cell densities than unlesioned juncos in the hippocampus and SVZ. Lesioned chickadees showed injury induced cell incorporation only in the injured hippocampus. However, lesioned juncos showed significantly higher BrdU-IR cell densities in both the injured and intact hemispheres of the hippocampus and pSVZ. Unlike juncos, chickadees therefore showed a highly localized response to injury. These results may indicate that during the fall food storers: (1) inhibit injury-induced cell birth and/or incorporation; (2) are incapable of further increases in cell birth or incorporation; or (3) have a much faster turnover of newly born cells resulting in fewer cells after 7 days.
Hippocampus and septum volumes show season, sex, and species differences in Black-capped Chickadees and Dark-eyed Juncos.
Mitterling, K. L., Law, L. M., Gardner, R. D., Ramus, S. J., Lee, D. W. (2007). Society for Neuroscience Abstracts
Development of norms and psychometric analysis of the Beck Depression Inventory-II in reference to chronic pain patients: A proposed study.
Pierce, R. S., Gardner, R. D., & Lopez, M. N. (2006). Poster presented at California State University, Long Beach during the Psi-Chi student research poster fair.