On innate behaviors : focus on parental behavior and aggression

The neural substrates orchestrating a number of social behaviors, including parental behavior and aggression, are known to exist in the hypothalamus. Through the control of the pituitary gland, the hypothalamus regulates the release of a number of hormones necessary for the physiological control of bodily functions and the expression of appropriate behaviors. In recent years the neuroscience community has invested large resources in identifying, through molecular markers, subsets of neurons whose activity impacts behavioral expression. This approach, however, has several weaknesses, among which is the assumption that a neuron’s function and output adhere to generalized principles. Consequently, such investigations often fail to identify the intricate organization of neural networks, which adapt the neural code in order to tune a system’s output to the behavior it modulates.

The aim of this thesis is to expand on basic neurophysiological concepts regarding the complex organization within and among neural groups. Here we addressed the principles of how a set of neurons self-tune their activity through the use of their own neurotransmitter, intra- and inter-network connectivity designs and spike rate coding of neurotransmitter release. Following this interrogation of neural network properties, we attempted to link the activity of these neural nodes to behavioral output, where we identified two distinct subsets of neurons driving parental behavior and aggression respectively.

In paper I, we performed a study on the properties of autoregulation in a neural network, and identified the ionic mechanisms through which the tuberoinfundibular dopamine (TIDA) neurons control their own activity via the use of their own neurotransmitter, dopamine (DA). In paper II, we encountered an unexpected species difference in baseline activity and oscillation frequency between rat and mouse TIDA neurons. Following an in-depth investigation, we attributed this difference to the presence vs complete absence of electrical coupling in the rat and mouse TIDA cells respectively. This generated the question of how different modes of TIDA neuron activity impact DA release at their terminals, which was addressed in paper III where, using fast-scan cyclic voltammetry, we performed the first investigation coupling patterns of electrophysiological activity to DA release in the TIDA system. In paper IV we addressed the possibility that this discrepancy in TIDA neuron activity has a behavioral impact. Following a step-by-step breakdown of the lactotropic axis in the male rat and mouse, we ultimately provided a link between TIDA neuron activity and the suppression vs expression of paternal behavior in the two species.

The final part of this thesis includes two studies focusing on aggressive behavior. In paper V, we performed a functional interrogation of a subset of ventral premammillary (PMv) neurons involved in intermale aggression, while in paper VI we identified that the very same neurons are activated by maternal hormones and modulate the expression of maternal aggression in lactating female mice.

Overall, the work presented in this thesis provides a step forward in our understanding of neural function and on the neural substrates underlying social behavior.

List of scientific papers

I. Stagkourakis S, Kim H, Lyons DJ, Broberger C. Dopamine Autoreceptor Regulation of a Hypothalamic Dopaminergic Network. Cell reports. April 2016, 15:735-747.
https://doi.org/10.1016/j.celrep.2016.03.062

II. Stagkourakis S, Pérez CT, Hellysaz A, Ammari R, Broberger C. Network oscillation rules imposed by species-specific electrical coupling. eLife. May 2018, 7:1-18.
https://doi.org/10.7554/eLife.33144

III. Stagkourakis S, Dunevall J, Taleat Z, Ewing A, Broberger C. Dopamine release dynamics in the tuberoinfundibular dopamine system. [Manuscript]

IV. Stagkourakis S, Williams P, Kakadellis S, Ziegler K, Bakker J, Harkany T, Broberger C. Neurohormonal basis of paternal behavior. [Manuscript]

V. Stagkourakis S, Spigolon G, Williams P, Protzmann J, Fisone G, Broberger C. A neural network for intermale aggression to establish social hierarchy. Nature Neuroscience. May 2018, 21:834-842.
https://doi.org/10.1038/s41593-018-0153-x

VI. Stagkourakis S, Williams P, Spigolon G, Ziegler K, Heikkinen L, Fisone G, Broberger C. Control of maternal aggression via maternal-hormone sensitive hypothalamic neurons. [Manuscript]