Application of midbrain dopamine in neuronal circuits regulating humoral balance

Water and food have rewarding properties, primarily because they satisfy the body's intrinsic needs

On July 13, 2022, the research team of Zachary A.

Figure 1: Endoscopic recording of VTA-DA neuronal activity

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Interestingly, the time window for this delayed response coincides with the time window for water integration into the blood for systemic rehydration, suggesting that systemic rehydration induces delayed activation of VTA-DA neurons

Most of the VTA-DA neurons in mice were activated and a few were inhibited after ingestion of aqueous solution, but most VTA-DA neurons were inhibited and a small part were activated after ingestion of hyperosmolar solution, and in the lower blood VTA-DA neurons hardly responded to volume or blood pressure, suggesting that VTA-DA neurons play an important role in body fluid balance in response to changes in body osmotic pressure

Direct intragastric perfusion of aqueous solution or intraperitoneal injection of aqueous solution can induce delayed responses in VTA-DA neurons

Figure 2: Upstream neural circuits that regulate fluid balance

Previous studies have shown that inhibitory neurons in the lateral hypothalamus (LH) that regulate feeding behavior project to VTA-DA neurons (hereafter referred to as LH-GABA→VTA)

In addition, after photoactivation of the LH-GABA→VTA circuit, inhibitory neuron activity in the VTA region was continuously inhibited, suggesting that aqueous solution intake could indirectly inhibit the activity of inhibitory neurons in the VTA region through this circuit, thereby increasing the activity of DA neurons

Figure 3: Downstream neural circuits that regulate fluid balance

Subfornix organ (SFO) glutamatergic neurons can encode fluid balance information and regulate thirst, this brain region is upstream of the LH, and chronic activation of glutamatergic neurons in the SFO region does not affect VTA-DA neurons activity, but enhanced VTA-DA neuronal activity induced by water intake

In order to further explore the downstream regions of VTA-DA neurons in regulating the function of humoral balance, the researchers found that VTA-DA neurons project to the inferior limbic prefrontal cortex (IL), basolateral amygdala (BLA), dorsal striatum (DS) and nucleus accumbens (NAc)

Generally, food or water enters the gastrointestinal tract and then into the bloodstream by mouth

Collectively, this paper reveals that dopaminergic neurons in the ventral tegmental area of ​​the midbrain track body fluid changes and regulate fluid balance through distinct neural circuits: lateral hypothalamic inhibitory neurons integrate humoral encoding from subfornix organs Balance information and transmit to dopaminergic neurons in the ventral tegmental area

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