Synaptic potentiation onto habenula neurons in learned helplessness model of depression

By Bo Li, J. Piriz, Martine M. Mirrione, ChiHye Chung, Christophe D. Proulx, D. Schulz, F. Henn, R. Malinow. Nature, 2011

607 citations recorded by the source corpus.

The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal’s helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/2e5ab39b83b8928ff74036e7cc70e4a94b891868

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. S. Lammel
2. R. Malenka
3. B. Lim
4. Gina G. Turrigiano
5. S. Hyman
6. E. Nestler
7. Wolfram Schultz
8. Raphael Cohn

In Cognitive Neuroscience

1. S. Lammel
2. R. Malenka
3. B. Lim
4. S. Hyman
5. Gina G. Turrigiano

Citations in the corpus

• Reward and aversion in a heterogeneous midbrain dopamine system (2013, background): “The potential involvement of the LHb in depression (Li et al., 2011; Morris et al., 1999; Shumake and Gonzalez-Lima, 2003) and the specific synaptic connectivity of LHb inputs in the VTA (Hikosaka, 2010; Lammel et al.”
• Input-specific control of reward and aversion in the ventral tegmental area (2012, unknown): “Further elucidation of the detailed synaptic connectivity of LHb inputs to VTA may be particularly interesting in the context of the potential role of LHb in psychiatric disorders such as depression and schizophrenia 18, 35-37 .”
• Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences (2016, unknown): “The second PC, by contrast, revealed a specific correlated group of DORpm (polymodal association cortex-related dorsal thalamus) regions, containing the lateral habenula (LHb), a key nucleus for aversive behaviors (Li et al., 2011, 2013).”