Physiological characteristics of the projection pathway from the medial preoptic to the nucleus raphe magnus of the rat and its modulation by the periaqueductal gray.

Anatomical studies have shown a strong projection from the medial preoptic nucleus of the hypothalamus (MPO) to both the periaqueductal gray (PAG) and nucleus raphe magnus (NRM). In this study, we examined the physiological characteristics of MPO to NRM connections and examined how blockade of neuronal transmission and of the glutamatergic system within the PAG modifies this pathway. In deeply anesthetized rats, recordings were made from NRM neurons that were identified by their response to peripheral mechanical stimulation and designated as "E", "I", or "N" if they were excited, inhibited, or not activated by noxious stimulation. In addition, cells were identified as spinally projecting if they could be antidromically activated by stimulation of the dorsolateral funiculus at the thoracic level. The responses of 204 NRM neurons to electrical and 87 cells to both chemical and electrical stimulation of MPO were recorded. The response of NRM neurons to MPO stimulation was highly dependent on the sensory class of these cells. Chemical stimulation of MPO inhibited 50% (16/32) and excited 16% (5/32) of the I-cells. In contrast, 23% (9/39) of the E-cells were inhibited and 49% (19/39) were excited by chemical stimulation of MPO. Electrical stimulation at intensities below 80 microA at 100Hz had similar effects on the two classes of cells; 62% (24/39) of the E-cells and 31% (10/32) of the I cells were excited, and 31% (12/39) of the E-cells and 59% (19/32) of the I-cells were inhibited. The excitatory response to chemical stimulation lasted for an average of 136.8+/-73.2s and inhibitory response lasted for an average of 143.8+/-102.1s. Electrical stimulation of MPO at 1Hz excited 27%, inhibited 3%, and had no effect on 70% of NRM cells. The mean latency to peak excitation was 9.6+/-6.6ms. Antidromic activation of MPO neurons by NRM stimulation showed an average latency of 6.3+/-3.4ms. Blocking the glutamatergic transmission within the PAG (by injecting kynurenic acid (KYN) into the PAG) blocked the inhibitory response of 40% (6/15) of the I-cells and inhibitory response of 43% (3/7) of the E-cells. The excitatory response of 27% (3/11) of the I-cells and the excitatory response of 14% (1/7) of the E-cells were blocked by kynurenic injection into the PAG. It is concluded that: (1) in response to chemical stimulation of MPO, the number of I-cells that were inhibited was more than three times the number of I-cells that were excited; in contrast, the number of E-cells that were excited was more than twice the number of E-cells that were inhibited. (2) The interaction between MPO and NRM can be modulated by blockade of the neuronal transmission or blockade of the glutamatergic system in the PAG. (3) Simultaneous activity of many synapses is required for activation of the MPO-NRM pathway. (4) MPO to NRM interaction is mediated by fibers with a conduction velocity of less than 1m/s.