The spinal GABA system modulates burst frequency and intersegmental coordination in the lamprey: differential effects of GABAA and GABAB receptors.
1. The effect of spinal GABAergic neurons on the segmental neuronal network generating locomotion has been analyzed in the lamprey spinal cord in vitro. It is shown that gamma-aminobutyric acid (GABA)A- and GABAB-mediated effects influence the burst frequency and the intersegmental coordination and that the GABA system is active during normal locomotor activity. 2. Fictive locomotor activity was induced by superfusing the spinal cord with a Ringer solution containing N-methyl-D-aspartate (NMDA, 150 microM). The efferent locomotor activity was recorded by suction electrodes from the ventral roots or intracellularly from interneurons or motoneurons. If a GABA uptake blocker was added to the perfusate, the burst rate decreased. This effect was counteracted by GABAB receptor blockade by phaclofen or 2-(OH)-saclofen. If instead a GABAB receptor agonist (baclofen) was added during fictive locomotion, a depression of the burst rate occurred. It was concluded that a GABAB receptor activation due to an endogenous release of GABA caused a depression of the burst activity with a maintained well-coordinated locomotor activity. 3. If a GABAA receptor antagonist (bicuculline) is applied during fictive locomotion elicited by NMDA, a certain increase of the burst rate occurred. Conversely, if a selective GABAA agonist (muscimol) was administered, the burst rate decreased. Similarly, if the GABAA receptor activity was potentiated by activation of a benzodiazepine site by diazepam, the burst rate was reduced. If, however the GABAergic effect was first enhanced by an uptake blocker (nipecotic acid), an administration of a GABAA antagonist (bicuculline) increased the burst rate, but in addition, the burst pattern became less regular with recurrent shorter periods without clear reciprocal burst activity. The GABAA receptor activity appears important for the rate control and for permitting a regular burst pattern. 4. The intersegmental coordination in the lamprey is characterized by a rostrocaudal constant phase lag of approximately 1% of the cycle duration between the activation of consecutive segments during forward swimming. This rostrocaudal phase lag can be reversed during backward swimming, which can be induced also experimentally in the isolated spinal cord by providing a higher excitability to the caudal segments. In a split-bath configuration, a GABA uptake blocker or a GABAB agonist was administered to the rostral part of the spinal cord, which caused a reversal of the phase lag as during backward swimming. If GABAA receptors were blocked under similar conditions, the intersegmental coordination became irregular. It is concluded that an increased GABA activity in a spinal cord region can modify the intersegmental coordination.(ABSTRACT TRUNCATED AT 400 WORDS)
Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm, Sweden.
J
J
Tegnér
T
T
Matsushima
A
A
el Manira
S
S
Grillner
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D046508:Culture Techniques; D003975:Diazepam / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D018756:GABA Antagonists; D007798:Lampreys / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009132:Muscles / Q000294:innervation; D016202:N-Methylaspartate / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009557:Nipecotic Acids / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011963:Receptors, GABA-A / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000145:classification / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018756:GABA Antagonists; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C052329:phaclofen; C030278:nipecotic acid; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D011392:Proline; C010983:homoproline; D001418:Baclofen; D003975:Diazepam; D001640:Bicuculline