DRN neuronal activity in response to pharmacological agents provides valuable insights into drug mechanisms of action. For instance, chronic administration of an antidepressant, Citalopram, a selective serotonin reuptake inhibitor (SSRIs) has been shown to potentiate the spontaneous activity of DRN serotonergic neurons. On the contrary, inhibition of the spontaneous activity of DRN deepened the anesthesia and prolonged the emergence time during general anesthesia and may have implications for anxiolytic or sedative properties.
Serotonergic neurons in the dorsal raphe nucleus (DRN) are typically mostly silent under physiological conditions. Their activity is regulated by norepinephrine (NE) released from noradrenergic projections originating in the locus coeruleus (LC), which activate α1-adrenoceptors. Consequently, the application of phenylephrine can enhance the firing activity of serotonergic neurons in the DRN.
These neurons also exhibit auto in hibition through 5-HT1A autoreceptors. Therefore, the increased activity induced by phenylephrine, combined with the inhibition from ipsapirone (a 5-HT1A agonist), provides an effective method for isolating the activity of serotonergic neurons in the DRN.
NMDA also elevates activity in the DRN, without being specific to serotonergic neurons. However, this activity can be differentiated by sorting electrodes that are sensitive to ipsapirone.
Multielectrode arrays (MEAs) provide a powerful platform for studying the dorsal raphe nucleus (DRN) activity, allowing to square the nucleus with up to 30 recordings electrodes. The serotonin neurons activity can be isolated using specific tool compounds. Such capabilities are valuable for depression, anxiety, and addiction research, as well as for target validation.
Spikes detection
The raw data is filtered with a high pass filter (Butterworth second order filter, set at 200 Hz). The threshold for detecting spikes is set to 4 standard deviations of the baseline noise assessed during TTX period
Phenylephrine enhance serotoninergic neurons activity in DRN, while 5-HT1A mediate autoinhibition
NMDA Enhances DRN Firing; Ipsaspirone as a tool compound to Isolate Serotonergic Neuron activity
Serotonergic neurons in the dorsal raphe nucleus (DRN) are typically mostly silent under physiological conditions. Their activity is regulated by norepinephrine (NE) released from noradrenergic projections originating in the locus coeruleus (LC), which activate α1-adrenoceptors. Consequently, the application of phenylephrine can enhance the firing activity of serotonergic neurons in the DRN.
These neurons also exhibit autoinhibition through 5-HT1A autoreceptors. Therefore, the increased activity induced by phenylephrine, combined with the inhibition from ipsapirone (a 5-HT1A agonist), provides an effective method for isolating the activity of serotonergic neurons in the DRN.
NMDA also elevate activity in the DRN, without being specific to serotonergic neurons. However, this activity can be differentiated by sorting electrodes that are sensitive to ipsapirone.
Multielectrode arrays (MEAs) provide a powerful platform for studying the dorsal raphe nucleus (DRN) activity, allowing to square the nucleus with up to 30 recordings electrodes. The serotonin neurons activity can be isolated using specific tool compounds. Such capabilities are valuable for depression, anxiety, and addiction research, as well as for target validation.
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