Biomedical subjects
Kelly G Lambert
Publications and source records attributed to Kelly G Lambert.
Rising rates of depression in today's society: consideration of the roles of effort-based rewards and enhanced resilience in day-to-day functioning.
Despite the existence of a vastly improved health care system and a multi-billion dollar antidepressant industry, the rates of depression in the US remain alarmingly high. An exploration of lifestyle changes over the past century suggests that the level of physical activity necessary to provide life's basic resources, referred to as effort-based rewards, has diminished in our industrialized, technologically advanced, service-oriented society. The evolution of the accumbens-striatal-cortical circuitry and its modulating neurochemicals in our ancestors played a significant role in sustaining the continued effort critical for the acquisition of resources such as food, water and shelter; consequently, vast reductions in the degree of physical activity required to obtain necessary resources in today's society likely lead to reduced activation of brain areas essential for reward/pleasure, motivation, problem-solving, and effective coping strategies (i.e. depressive symptomology). Comparative cultural and gender analyses reinforce the significant role of effort-based rewards in mood regulation, suggesting that minimal engagement in such endeavors leads to compromised resilience upon exposure to life's stressful challenges. If physical activity is indeed important in the maintenance of mental health, increased emphasis on behavioral and behavioral/cognitive preventative life strategies, as opposed to an emphasis on psychopharmacological strategies directed at very specific neurochemicals after the onset of depression, should be adopted as protective measures against the onset of depressive symptomology. Thus, strategies that include more global neurobiological activation in the relevant context of directed efforts provide a fresh perspective for depression research.
Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat.
The current work examined spatial learning and memory (i.e., latencies to find a baited food well) in age-matched nulliparous, primiparous and multiparous (NULL, PRIM and MULT, zero, one or two pregnancies and lactations, respectively). We tested at 6, 12, 18 and 24 months of age in a dry land version of the Morris water maze (Main task), and at 12, 18 and 24 months in the same task in which the original location of the baited well was changed (Reversal task). We show that PRIM/MULT rats, compared to the age-matched NULL females, learned the spatial tasks significantly better and exhibited attenuated memory decline, up to 24 months of age. Furthermore, at the conclusion of behavioral testing, we investigated levels of these animals' hippocampal (CA1 and dentate gyrus) immunoreactive amyloid precursor protein (APP), a marker of neurodegeneration and age-related cognitive loss. MULTs had significantly reduced APP in both CA1 and DG, relative to PRIMs and NULLs, and PRIMs had a trend (p<0.06) toward a reduction in APP compared to NULLs in DG. Further, level of APP was negatively correlated with performance in the two tasks (viz., more APP, worse maze performance). Reproduction, therefore, with its attendant natural endocrine and postpartum sensory experiences, may facilitate lifelong learning and memory, and may mitigate markers of neural aging, in the rat. Combining natural hormonal exposure with subsequent substantial experience with stimuli from the offspring may preserve the aged parous female brain relative to that of NULL females.
Motherhood and the hormones of pregnancy modify concentrations of hippocampal neuronal dendritic spines.
Short-term fluctuations in steroid hormones such as estradiol (E2) and progesterone (P) can affect the concentration of hippocampal dendritic spines in adult, cycling nulliparous female rats. Pregnancy is characterized by a significantly longer duration of substantially elevated E2 and P compared to the estrous cycle. Thus, even greater changes than those reported during estrus may be evident. In two experiments, we examined the extent to which reproductive and hormonal state altered the concentration of apical neuronal dendritic spines of the CA1 region of the hippocampus in the following age-matched groups (N's = 7-10/group) of rats: in Exp. 1., CA1 dendritic spine density was examined in nulliparous diestrus (DES), proestrus (PRO), and estrus (ES) females, and late-pregnant (LP) (day 21) and lactating (day 5-6; LACT) females. In Exp. 2, the effects on spine density of a regimen mimicking pregnancy (and that stimulates maternal behavior) were examined, using ovariectomized, no hormone-exposed (OVX-minus) vs. sequential P&E(2)-treated (OVX + P&E2) groups. For both experiments, brains were removed, Golgi-Cox-stained and the most lateral tertiary branches of the apical dendrite of completely-stained hippocampal CA1 pyramidal neurons were traced with oil-immersion at x 1600 and dendritic spine density (# spines/10 micro dendritic segment) recorded. In Exp. 1, spine density was increased in LP and LACT females (which were not different) compared to the other virgin groups, including PRO females, who had more spines than DES and ES. In Exp. 2, OVX + P&E2 displayed significantly more dendritic spines per 10 micro than OVX-minus females (and had numbers that were similar to those of LP and LACT from Exp. 1). Pregnancy and its attendant hormonal fluctuations, therefore, may alter hippocampal neurons that regulate some non-pup-directed components of maternal behavior (e.g., nest building) or behaviors that support maternal behavior (e.g., foraging, associative memory).
Maternal experience produces long-lasting behavioral modifications in the rat.
From 5 to 22 months of age, cognitive and emotional responses of nulliparous, primiparous, and multiparous rats were assessed using a dry land maze (DLM) and an elevated plus-maze (EPM) at 4-month intervals. Parous rats exhibited improved spatial memory in the probe and competitive versions of the DLM, and more exploration in the EPM and a novel stimulus test relative to nulliparous females. The nulliparous females, however, outperformed parous rats during the DLM visual cue test at 17 months of age. At 23 months, no differences in stressed corticosterone levels or Golgi-stained hippocampal neurons were observed. Thus, cognitive and emotional modifications were observed in parous rats; the neurobiological mechanisms for these enduring effects, however, remain to be identified.
The life and career of Paul MacLean. a journey toward neurobiological and social harmony.
Working as a physician, Paul MacLean's interests moved in the direction of the brain when he realized that most of his patients suffered from symptoms (e.g. anxiety, sleeping problems) that could not be traced to a known physiological cause. His curiosity about the neurological origins of these psychological symptoms led him to the laboratories of Stanley Cobb and James Papez, both of whom were influential in guiding MacLean's interests toward the temporal lobe. His neurobiological interest was not contained, however, to the temporal lobe. As his own family grew to include a wife and five children, his scholarly pursuits extended to social and familial relations and their accompanying underlying neuroanatomical circuits (i.e. the thalamocingulate system). Viewing the brain and behavior from an evolutionary perspective, MacLean introduced the concept of the "triune brain" to describe the evolutionarily distinct components of the mammalian brain and reintroduced Broca's term "limbic" to describe a neuroanatomical system involved in emotional functions. MacLean wrote that the development of social behaviors, such as mother-infant audiovocal communication and the separation cry of the offspring, served as the driving force in the evolution of the neocortex. MacLean's neuroevolutionary perspective and appreciation of the complexity and evolutionary significance of social systems offer valuable insights into the contemporary fields of behavioral neuroscience and biological psychiatry.
Single or multiple reproductive experiences attenuate neurobehavioral stress and fear responses in the female rat.
The female brain is a dynamic structure, which expresses its plasticity most readily following reproductive experience (RE). In Experiment 1, we generated nulliparous (NP), primiparous (PP), and multiparous (MP) females (none, one, and two litters, respectively). Two weeks following the weaning of the first/second six-pup litters, the age-matched MP and PP and the non-pup-exposed NP animals were subjected to a 60-min restraint stress paradigm (enclosure in a Plexiglas restraint tube). The brains were removed and processed for c-fos immunoreactivity (c-fos-IR) in CA3 region of the hippocampus (HI) and in basolateral amygdala (BLA). MP and PP females had very similar numbers of c-fos-IR neurons in both HI and BLA, whereas both were lower than NPs. In a second experiment, the same groups were generated, together with primigravid (PG; first pregnancy) and multigravid (MG; second pregnancy) females, tested in late pregnancy. The animals were exposed to a 30-min trial in an open field and were killed, and the brains were again examined for c-fos-IR. The parous and gravid animals displayed less reactivity to the stress of the open field (i.e., reductions in behavioral measures of anxiety) and significantly less c-fos expression in both CA3 and BLA. The gravid animals displayed significantly less c-fos expression in CA3 and BLA compared to parous females, although neither group differed as a result of a second RE. The data suggest that reproductive (viz., hormonal) and/or maternal (viz., pup exposure) experience may inure a female and her brain to stress, rendering her less susceptible to the behavioral-or other-disruptions that stress sensitivity can produce. Together, these data suggest that the experiences of motherhood (pregnancy, pup exposure, suckling stimulation, etc.) summate to produce reductions in anxiety and stress responsiveness that start before and last long after pup exposure and care. Such reductions may be adaptive in the face of demands placed upon the parous vs. the NP female.