The modulatory function of the LHb in depression is intensively investigated by neuroscientists at the moment. The LHb is a structure located ventral in the diencephalon at the stalk of the pineal gland and is thought to be a regulator of monoaminergic brain regions (Geisler et al., 2008). The misregulation of monoamines in the brain is tightly connected to the altered neurotransmission seen in depression, this is known as the monoaminergic theory of depression (Skolnick, 2002). More specifically, 5-HT deficiency may impair antidepressant responses (Sachs et al., 2015). The hyperactivity of the LHb is associated with depression (Wirtshafter et al., 1994). The LHb is tightly affiliated to the motivational and reward system via connections with
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Furthermore, increased LHb activity is involved in the inhibition of dopaminergic neurons, suggesting a regulatory role of the LHb in the reward system (Stamatakis et al., 2013). Converging evidence on this systematic can be found in a study where the habenula is pharmaceutically inhibited, leading to increased DA levels (Lecourtier et al., 2008), presumably via disinhibition of midbrain structures via the RMTg (Stamatakis et al., 2012). Additionally, electrical stimulation of LHb with DBS led to increased monoamine concentrations in depressed rats (Meng et al., 2011). Significant elevations of 5-HT levels was found after LHb DBS, as compared with levels of NE and DA, suggesting a close correlation between the activity of the LHb and serotonergic neurotransmission (Meng et al., 2011). Additionally, DRN neurons are theorized to interfere with excitatory VTA and EP projections towards the LHb to organize reward behavior via serotonergic and glutamate projections (Liu et al., 2015; Nair et al., 2013). Decreasing output of the LHb could result in increased resistance to the effects of stress and provide a rationale for inhibition via DBS in severely depressed patients (Mirrione et al,
Furthermore, increased LHb activity is involved in the inhibition of dopaminergic neurons, suggesting a regulatory role of the LHb in the reward system (Stamatakis et al., 2013). Converging evidence on this systematic can be found in a study where the habenula is pharmaceutically inhibited, leading to increased DA levels (Lecourtier et al., 2008), presumably via disinhibition of midbrain structures via the RMTg (Stamatakis et al., 2012). Additionally, electrical stimulation of LHb with DBS led to increased monoamine concentrations in depressed rats (Meng et al., 2011). Significant elevations of 5-HT levels was found after LHb DBS, as compared with levels of NE and DA, suggesting a close correlation between the activity of the LHb and serotonergic neurotransmission (Meng et al., 2011). Additionally, DRN neurons are theorized to interfere with excitatory VTA and EP projections towards the LHb to organize reward behavior via serotonergic and glutamate projections (Liu et al., 2015; Nair et al., 2013). Decreasing output of the LHb could result in increased resistance to the effects of stress and provide a rationale for inhibition via DBS in severely depressed patients (Mirrione et al,