In 2267, the automatic scanner of the Galileo detected a space anomaly. The shuttle's sensors registered the anomaly as something resembling vaguely an ionized hydrogen cloud with erratic energy readings. This "cloud" was traveling at warp speed. (TOS: "Metamorphosis")
In 2268, as the USS Enterprise searched for a missing landing party, Ensign Jana Haines reported that the sensors were registering fluctuating energy readings from a hydrogen cloud. Although faint, each reading consistently demonstrated an excess of predictable energy level. Aided by the ship's computer, Spock determined that an ionization trail would account for this and that there was no explanation known to Federation science to account for the trail. He then ordered a follow course. (TOS: "The Gamesters of Triskelion")
Later that year, James T. Kirk proposed a reflection from a hydrogen cloud as the cause of an anomalous sensor reading. Spock however dismissed the possibility as there were no hydrogen clouds nearby. (TOS: "Elaan of Troyius")
In 2372, the USS Voyager was hailed by a probe emitting a Federation signal in the Delta Quadrant. The signal originated from inside a hydrogen cloud. Voyager arrived at the hydrogen cloud, but it was later found that the Kazon were hiding there in order to overwhelm Voyager's defenses, due to the traitor Seska providing the Kazon-Nistrim Voyager's access codes. The Kazon were ultimately successful in stealing a transporter oscillator from the ship. (VOY: "Maneuvers")
In the shooting script of Star Trek: The Motion Picture, the film would have begun in deep space. After witnessing a supernova, the camera would move on searching for V'ger. In its search, the camera would have seen "swirling hydrogen clouds".