Research Interests

Broadly, I am interested in how hormones affect the brain and the behavior of animals, and how these relationships have evolved across species. I am also interested in how sensory processing interacts with neuroendocrine systems to affect behavioral outcomes. My Ph.D. work focused on the role of the hormone prolactin in avian parental care behavior and my post-doctoral work examined the role of prolactin in paternal behavior in rodents. I have recently started a new line of research which seeks to understand how hormones affects sensory processing in parents during behavioral interactions with offspring. My goal is to develop a comparative neuroendocrinology research program which seeks to understand various sensory-hormone-behavior relationships across vertebrates. 

I will be starting my own in lab in January 2025 in the Biopsychology Department at the University of Michigan. which will study the neural, hormonal, and sensory basis of parental behavior!

Read more below on the various types of research I’ve done in the past.

Neural processing of offspring auditory cues in parental and non-parental zebra finches (2022- Present)

Recording a day 6 old chick’s begging call into a microphone.

In-vivo electrophysiology recording of a single unit in an adult bird listening to a begging call. Top panel is a raster plot of spike activity 2 seconds before the stimulus onset, during the 4 second playback (pink), and 2 seconds after the offset of the stimulus. Bottom panel is an average instantaneous firing rate activity across the stimulus period described above. Spectrogram of begging call played is above the top panel.

For many species, auditory cues unique to dependent offspring, such as baby cries, elicit the necessary parental behavior responses in adults. Despite this, we know little about how the brain encodes offspring auditory cues or how these cues are used to elicit parental responses. Zebra finches are an excellent model to study the neural encoding of offspring calls. Both male and female parents raise the young and rely on auditory cues (begging calls) to elicit chick feeding responses (parental behavior). Begging calls become individually identifiable by the parents, necessitating higher-order learning/association neural processes. The caudomedial nidopallium (NCM; analogous to the mammalian secondary auditory cortex), is involved in the perception of complex auditory signals. Therefore, I hypothesize that NCM is necessary to properly unpack and interpret offspring sensory stimuli, leading to fulsome parental responses. To begin testing this, we used IEG and in vivo electrophysiology studies to show that NCM responds to begging calls. I am currently testing whether NCM responded to begging calls differently in parents and non-parents. This work will lay the essential ground-work for further testing of how hormones may modulate auditory responses in parents. I am currently doing this work in Luke Remage-Healey’s lab at UMass Amherst.

Funding:

NIH K99/R00 BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity, 1 K99 HD108800-01 (2022-Present)

Role of mating, prolactin, and neurogenesis in the transition to paternal care (2020-2022)

Prolactin increases cell proliferation in the SVZ in recently mated males. Mated males that received a prolactin rescue injection had more BrdU positive cells in the dorsal and lateral regions of the rostral and the caudal SVZ relative to the control and bromocriptine (bromo, a prolactin suppressor) treated males. Data from Smiley et al., 2023 Front Behav Neuro.

A remaining important but unanswered question is what changes occur at mating (the social stimulus required for mouse paternal care) that allow for the transition from attacking to parental behavior in male mice? During pregnancy, prolactin stimulates neurogenesis in the olfactory bulb, which is essential for maternal behavior. Mating induces olfactory neurogenesis in males, but it is unknown whether this is driven by prolactin or is important for subsequent paternal care. New neurons are generated from cells in the subventricular zone (SVZ) and take about two weeks to migrate to the olfactory bulb, which may account for the delayed behavioral change in mated males. To begin testing this hypothesis, we tested whether mating increases cell proliferation at the SVZ. Males were either mated, exposed to receptive female cues, or left alone (control) and injected with BrdU (a marker of cell division). In contrast to our hypothesis, we found that mating had no effect on cell proliferation at the SVZ. Next, we tested whether prolactin mediates cell proliferation during mating by administering bromocriptine (prolactin inhibitor), vehicle, or bromocriptine+prolactin prior to mating. While suppressing prolactin had no effect, administering exogenous prolactin resulted in significantly higher BrdU-labelled cells in the SVZ. Taken together, mating may have greater effects on new olfactory cell survival, as opposed to SVZ cell proliferation, and propose that mating-induced prolactin may have downstream effects on olfactory cell survival.

Relevant Papers

1.     Smiley, K.O.*, Phillipps, H.R., Fang, C., Brown, R.S.E., Grattan, D.R., 2023. Mating-induced prolactin surge is not required for subsequent neurogenesis in male mice. Frontiers in Behavioral Neuroscience 17, 1227726. https://doi.org/10.3389/fnbeh.2023.1227726 *Invited author for Special Issue: Plasticity and Flexibility in the Parental Brain.

Funding:

Marsden Fund Fast Start Grant, Royal Society of New Zealand, 20-UOO-110 (2020-2022)

University of Otago Division of Health Sciences Postdoctoral Fellowship (2020-2022)   

Prolactin and rodent paternal care (2018-2022)

Mated male mic with a the prolactin receptor knocked out of forebrain neurons (CKC, blue) show reduced pup retrieval behavior, relative to control males with functional prolactin receptors. Data from Smiley et al., 2022 J Neurosci.

Having established that prolactin is necessary for parental behaviors in both sexes of birds during my PhD, I decided to test whether prolactin is also involved in male parental behavior in mammals during my postdoc in Dave Grattan’s lab at the University of Otago. Male laboratory mice show a dramatic transition from attacking pups as virgins to caring for pups 3 weeks after mating (when pups are born). Using a Cre-mediated knock-out of the prolactin receptor localized to forebrain neurons, I showed that prolactin action in the brain is essential for the transition to paternal behavior in male mice. Males with a forebrain neuron-specific prolactin receptor knock-out show markedly reduced pup retrieval to the nest, one of the main parental behaviors displayed in mice. Using a conditional AAV-Cre-mediated deletion of the prolactin receptor in the medial preoptic area of the hypothalamus (MPOA; a region known for the regulation of parental care), I have shown that the expression of pup retrieval behavior is dependent on a population of prolactin-responding neurons in the MPOA.

Relevant Papers

1.     Smiley, K.O., Brown, R.S.E., and Grattan, D.R., 2022. Prolactin action in the brain is required for paternal care in the mouse. Journal of Neuroscience, 42 (44) 8308-8327. doi.org/10.1523/JNEUROSCI.0558-22.2022

2.     Stagkourakis, S., Smiley, K.O., Williams, P., Kakadellis, S., Ziegler, K., Bakker, J., Harkany, T., Brown, R.S.E., Grattan, D.R., and Broberger, C., 2020. A neuro-hormonal circuit for paternal behavior controlled by a hypothalamic network oscillation. Cell 182, 960-975. doi.org/10.1016/j.cell.2020.07.007

Funding:

British Society of Neuroendocrinology Project Support Grant (2019)                                                     

Prolactin receptors in the avian parental brain (2015-2017)

Prlr distribution in breeding (pink) and non-breeding (blue) zebra finch brains.

Prolactin has a well-established role in mediating mammalian maternal behavior through its actions on central prolactin receptors (Prlr). During my PhD, I develop a novel immunohistochemistry protocol in collaboration with Dr. Lynn Dong (Cornell Veterinary College) to visualize the distribution of central Prlr in the zebra finch brain. My research has provided the first detailed description of the central Prlr distribution in a songbird. Prlr are found in many areas relevant for parental behavior such as the medial preoptic area (MPOA), ventral tegmental area (VTA), and nucleus taeniae of the amygdala (TnA; avian homologue of the medial amygdala), all of which have been implicated in parental care. This work is an essential first step to facilitate future research that uses central PRL targets to manipulate parental behavior, and/or other physiological functions of prolactin.

 We also developed an immunohistochemistry protocol to visualize pStat5, a transcription factor that is expressed when the PRLR is activated, which serves as a reliable marker of recent PRLR activity. I compared pStat5 activity in breeding and non-breeding zebra finches and have found that areas such as the MPOA, VTA, and TnA show increased pStat5 staining in breeding birds, indicating these areas specifically activated by prolactin during parental care, a finding which is consistent with mammalian parental care (Smiley et al., 2020

Our paper made the cover of the journal! (Volume 301, 15 January 2021)

Relevant Papers

  1.     Smiley, K.O., Dong, L., Ramakrishnan, S., and Adkins-Regan, E., 2020b. Central prolactin receptor distribution and pStat5 activation patterns in breeding and non-breeding zebra finches (Taeniopygia guttata). General and Comparative Endocrinology, 301, 113657.

Funding:

NSF Doctoral Dissertation Improvement Grant, IOS 1501336,  DISSERTATION RESEARCH: Hormonal Regulation of Avian Biparental Care (2015-2017)

Treating male and female zebra finch parents with bromocriptine, a pharmacological suppressor of prolactin, drastically reduces parental behavior, including chick feeding behavior (red), relative to control parents which normally high circualting prolactin levels (black). Data from Smiley et al., 2018 Horm Behav.

The role of prolactin in avian parental care (2011-2017)

In most birds with altricial (immature) young, circulating prolactin levels are low during non-breeding times and significantly increase during late incubation and early post-hatch chick care.  Because of this pattern, prolactin has been suggested to be involved in the initiation of parental care in birds, but rarely has this hypothesis been tested. My dissertation work showed that blocking prolactin at the end of incubation and the beginning of post-hatch care either eliminated or drastically reduced parental care in both males and females. This is the first causal demonstration that prolactin is required in post-hatch parental care in both males and female zebra finches. My PhD advisor was Elizabeth Adkins-Regan, Psychology Department, Cornell University.

Relevant Papers:

1.     Smiley, K.O., and Adkins-Regan, E., 2018a. Lowering prolactin reduces post-hatch parental care in male and female zebra finches (Taeniopygia guttata). Hormones and Behavior, 98, 103–114.

2.     Smiley, K.O. and Adkins-Regan, E. 2016b. Prolactin is related to individual differences in parental behavior and reproductive success in a biparental passerine, the zebra finch (Taeniopygia guttata), General and Comparative Endocrinology, 234, 88-94.

3.     Smiley, K.O. and Adkins-Regan, E. 2016a. Relationship between prolactin and previous parental care experience in a biparental songbird, the zebra finch (Taeniopygia guttata), General and Comparative Endocrinology, 232, 17-24

4.     Smiley, K.O.* 2019. Prolactin and avian parental care: New hypotheses and unanswered questions. Hormones and Behavior, 111, 114-130. doi.org/10.1016/j.yhbeh.2019.02.012 *Invited reviewed for Young Investigators Award (Society for Behavioral Neuroendocrinology), Special Issue: Behavioral Neuroendocrinology: Current and Future Impact.

Funding:

NSF Doctoral Dissertation Improvement Grant, IOS 1501336,  DISSERTATION RESEARCH: Hormonal Regulation of Avian Biparental Care (2015-2017)