Dr. David Anderson: The Biology of Aggression, Mating, & Arousal

Dr. David Anderson explains that emotions are a subcategory of states which are driven by our nervous system and brain-body connections. Internal states like emotions, sleep, arousal, and motivation control behavior by changing the input-output transformation of the brain. Understanding emotions as a state puts the focus on it as a neurobiological process rather than a psychological one. Feeling is the tip of the iceberg, whereas emotions are a class of state that controls behavior. States can be broken down into different facets or dimensions. This understanding of emotions and states is important in studying mental health and mental illness, as it has direct implications for the future of mental health treatments.

Emotions have important properties like persistence and generalization that distinguish them from motivation states. Persistence is an important feature of emotion states and refers to their ability to outlast the stimulus that triggered them. Generalization is also an important component of emotion states that make them applicable to different situations. Arousal and valence are different axes that can be engaged by different neurochemicals and circuits. Different forms of arousal can be behavior-specific, which suggests that arousal is not unitary. Understanding how the components of states are encoded in the brain can open up a range of questions for research.

Aggression is not just an external behavior; it is also dependent upon an internal state that can be anger, fear, or hunger. Different types of aggression are generated by different neuro circuit mechanisms in the brain. Aggression can be stimulated by optogenetics in mice using specific neurons in the venture medial hypothalamus (VMH) region. The experiment does not work with electrical stimulation of mice because it activates fear neurons as well, which dominate aggression circuits. Offensive aggression, which is rewarding to male mice, can be triggered by the optogenetic stimulation of VMH in mice. Understanding the different types of aggression and their neural mechanisms can help us develop better solutions for controlling aggressive behaviors.

The state of aggressiveness is multifaceted, and it depends on the type of aggression and different circuits are involved. Some regions like the substantial in might be a final common pathway for all aggression. Offensive and defensive aggression can be difficult to differentiate. Defensive behaviors and fear arose before offensive aggression, which might be the reason why they are placed together in the circuitry. Animals first and foremost have to defend themselves from predation by other animals, and maybe it's only when they've warded off predation, they can start to think about who's going to be the alpha male in their group. The brain regions and cell populations might have evolved by duplication and modification.

Fear can inhibit offensive aggression while enhancing defensive aggression, and stimulating fear neurons can stop a fight dead in its tracks. Fear dominates over aggression hierarchically, but the exact mechanism of inhibition is unclear. The VMH has a role in controlling aggression and fear behaviors, but it also plays a role in metabolic functions. The intermingling of these functions may be important for the brain to prioritize and shut down specific behaviors. The concept of hydraulic pressure towards a state, such as sleep or anger, is multifactorial and complex, but understanding homeostatic behaviors can help break down and analyze this idea.

Our need-based behaviors work like a thermostat model of the brain where we have a set point. When we feel hungry, we need to eat, when we feel thirsty, we need to drink, and when we feel hot, we need to get to a cold place. The pressure that builds up is due to our need for something specific. However, aggression does not accumulate like that. Stronger activity in certain regions of the brain control aggression, mating, and feeding behaviors. When releasing aggression, it needs to be exerted on something. Similarly, the drive state generated by stimulating neurons in hypothalamus needs some external object to unplug it. Addiction to pornography can influence humans to abstain from seeking mates, but they resolve this issue on their own.

The internal state of a mouse whose VMH is being stimulated or a mouse whose brain other brain region that can stimulate the desire to mate for seeking and finding of sexual partners and or long term mates is different than prior to that stimulation. Presumably, there is arousal and neuroendocrine activation of stress response when the fear neurons that sit on top of the aggression neurons are activated up to genetically in the same way, in the animal. The neurons in VMH that control aggression are labeled with the estrogen receptor in male mice and other labs have shown that the estrogen receptor in adult male mice is necessary for aggression. Testosterone and estrogen play a role in generating aggression.

Female mice exhibit aggression only during nurturing and nursing their pups, while male mice are always aggressive. Estrogen and progesterone play a crucial role in aggression in male mice and likely in male humans. Females have a switch in the brain that changes their response from sex to aggression when becoming a mother, controlled by two subsets of estrogen receptor neurons. In fruit flies, both male and female have sex-specific fighting neurons, but females have a female-specific fighting neuron and a common neuron that activates the female-specific neuron. The complexity of sex-specific populations of neurons may be a mechanism of different behaviors between sexes.

Mating behavior in animals can involve aggression, but it's not always species or context specific. The brain regions controlling aggression and mating behavior are complex and interact with each other. Nursing mothers become aggressive to any intruder but it's unclear if lactation is required. The changes in hormones during pregnancy can make female rats aggressive to some extent but the biology of aggression and mating behavior is not fully explored. There are neurons in the VMH brain region that selectively activate during male-female mating encounters and may be involved in mating behavior. The brain regions controlling male sexual behavior are different from those controlling aggression and mating behavior.

The brain has interconnections between make love (mating) and make war (fighting) neurons, with some mutually inhibitory connections to prevent animals from attacking a mate during mating. Fetishes may represent repetitive conditioning where something aversive or disgusting is repeatedly paired with a rewarding experience, changing its valence, and producing anticipation of reward. Human neuroscience lacks tools to probe and manipulate neuro circuitry in this regard. The medial preop optic area contains neurons for mating and temperature regulation, which may relate to the menstrual/ether cycle. Understanding the complexities of the brain's wiring and interactions can shed light on primitive behaviors and motivations and their expression in human behavior.

The medial preop optic area contains different subsets of neurons that are active during different behaviors, including mating and aggression. Thermo regulatory neurons also exist in the area, which could be connected to energy expenditure and aggressiveness. Arousal and relaxation also play a significant role in the mating process. Mounting behavior can reflect dominance or sexual interactions, but it's difficult to distinguish between them since they look similar. While measuring body temperature can predict ovulation in women, relying on temperature alone for contraception is not recommended. Overall, this discussion highlights the intricate connections between various behaviors, systems, and regulators in the body, making it a fascinating and complex area of study.

Mounting behavior in male mice can be both reproductive and agonistic aggressive and can be distinguished based on whether it is accompanied by ultrasonic vocalizations or not. Different brain regions are maximally active during these different types of mounting. Animals display chasing and mounting behavior for different purposes, and the intent of such behavior may differ depending on individual and context. Female mice may also display male-type mounting behavior towards other females, and stimulating the same population of neurons in females as in males can evoke male-type mounting towards either a male or a female target. However, it is important to note that linking animal behavior to human behavior is inappropriate and dangerous, as humans possess additional neural circuitry and pathways that allow for context.

The periaqueductal gray (PAG) is a complex region in the brain that has been implicated in a range of innate behaviors, including fear, running away, freezing, mating, and pain modulation. PAG acts like an old-fashioned telephone switchboard, where different regions of the brain send projections to different sectors of the PAG. Neurons in these different sectors control different types of behavior when stimulated. PAG could be involved in endogenous analgesia, where animals do not feel pain when they are in a high state of fear, and this analgesia could be mediated by peptides in the adrenal gland. However, the mechanisms underlying pain modulation in the PAG still need to be fully understood.

Tachykinin, a neuropeptide that controls aggression and pain, is present in flies, mice, and humans. Social isolation increases the level of tachykinin in the brain, leading to an increase in aggression, fear, and anxiety. Drugs that block the receptor for tachykinin, such as Osanetant, have been shown to inhibit the effects of social isolation. Osanetant has a good safety profile in humans and has potential to be used for people who experience social isolation, stress, or bereavement stress. However, pharmaceutical companies are not always eager to test this drug despite its translational application in humans. Understanding the role of neuropeptides such as tachykinin can give insight into complex behaviors and may lead to the development of new therapies for emotional and physical pain.

Pharmaceutical companies are reluctant to retest drugs that have failed clinical trials due to the huge cost involved. However, many of these discarded drugs could be useful in treating other indications such as stress-induced anxiety or aggressive behavior. Dr. David Anderson believes that despite the fact that animal experiments with drugs may not always predict how humans will respond, there is good reason to think certain brain regions and molecules are evolutionarily conserved and would play a similar role in humans. Therefore, these drugs should be tested again on humans and even pets suffering separation anxiety to understand better their efficacy. It is essential to test and explore all possible medical treatments to support not just human welfare but also animal welfare.

Social isolation can drive powerful neurochemical and neurobiological changes, which researchers hope to explore further in the context of TKI kindin 1 and 2. The somatic marker hypothesis suggests that our subjective feelings of emotions are associated with sensations in certain parts of the body, such as the gut or heart. This bidirectional communication between the brain and body is mediated through the peripheral and central nervous systems and the vagus nerve. Understanding this mind-body connection is important for neuroscientists and the general population to accurately think about emotions and behaviors.

The vagus nerve is a bundle of nerve fibers that senses and influences the contraction of visceral organs like the heart and gut. Different vagal fibers control specific bodily functions, and researchers are just beginning to understand how they play a role in emotional states. Further study and technology development to turn on or off subsets of fibers within the vagus nerve could lead to a better understanding of mental illness and mental health treatments. The connection between the brain and body is vital not only for the gut but also for other organs, making it a central feature of emotional states.