homeostatic regulation

Keeping your Brain in Balance: the Ups and Downs of Homeostatic Plasticity (virtual)

Our brains must generate and maintain stable activity patterns over decades of life, despite the dramatic changes in circuit connectivity and function induced by learning and experience-dependent plasticity. How do our brains acheive this balance between opposing need for plasticity and stability? Over the past two decades, we and others have uncovered a family of “homeostatic” negative feedback mechanisms that are theorized to stabilize overall brain activity while allowing specific connections to be reconfigured by experience. Here I discuss recent work in which we demonstrate that individual neocortical neurons in freely behaving animals indeed have a homeostatic activity set-point, to which they return in the face of perturbations. Intriguingly, this firing rate homeostasis is gated by sleep/wake states in a manner that depends on the direction of homeostatic regulation: upward-firing rate homeostasis occurs selectively during periods of active wake, while downward-firing rate homeostasis occurs selectively during periods of sleep, suggesting that an important function of sleep is to temporally segregate bidirectional plasticity. Finally, we show that firing rate homeostasis is compromised in an animal model of autism spectrum disorder. Together our findings suggest that loss of homeostatic plasticity in some neurological disorders may render central circuits unable to compensate for the normal perturbations induced by development and learning.

The development of hunger

All mammals transition from breastfeeding to independent feeding during the lactation period. In humans and other mammals, this critical transition is important for later in life metabolic control and, consequently, for the development of many chronic conditions. Here, Dr. Dietrich will discuss the work of his lab studying the function of hypothalamic neurons involved in homeostatic control during the transition from breastfeeding to independent feeding. His work illuminates novel properties of hypothalamic neurons in early life, suggesting mechanisms by which early life events shape homeostatic regulation throughout the individual’s lifespan.

Spreading dynamics and homeostatic regulation in neural networks

Firing Homeostasis in Neural Circuits: From Basic Principles to Malfunctions

Neural circuit functions are stabilized by homeostatic mechanisms at long timescales in response to changes in experience and learning. However, we still do not know which specific physiological variables are being stabilized, nor which cellular or neural-network components comprise the homeostatic machinery. At this point, most evidence suggests that the distribution of firing rates amongst neurons in a brain circuit is the key variable that is maintained around a circuit-specific set-point value in a process called firing rate homeostasis. Here, I will discuss our recent findings that implicate mitochondria as a central player in mediating firing rate homeostasis and its impairments. While mitochondria are known to regulate neuronal variables such as synaptic vesicle release or intracellular calcium concentration, we searched for the mitochondrial signaling pathways that are essential for homeostatic regulation of firing rates. We utilize basic concepts of control theory to build a framework for classifying possible components of the homeostatic machinery in neural networks. This framework may facilitate the identification of new homeostatic pathways whose malfunctions drive instability of neural circuits in distinct brain disorders.

Homeostatic regulation of synaptic connectivity across connectomes

Bernstein Conference 2024

Homeostatic regulation through aggregate synaptic dynamics at multiple timescales

Bernstein Conference 2024

Homeostatic regulation of CA1 firing rate set points in response to chronic hyperactivation of interneurons