Subject(s)
Contact Lenses/adverse effects , Corneal Ulcer/diagnosis , Corneal Ulcer/etiology , Diabetes Complications/diagnosis , Uveitis/etiology , Anterior Chamber/pathology , Combined Modality Therapy , Corneal Ulcer/pathology , Corneal Ulcer/therapy , Diabetes Complications/therapy , Doxycycline/therapeutic use , Follow-Up Studies , Humans , Male , Middle Aged , Ophthalmologic Surgical Procedures/methods , Prednisolone/therapeutic use , Risk Assessment , Treatment Outcome , Uveitis/physiopathology , Uveitis/therapy , Vision Disorders/diagnosis , Vision Disorders/etiologyABSTRACT
Neuromodulators modify network output by altering neuronal firing properties and synaptic strength at multiple sites; however, the functional importance of each site is often unclear. We determined the importance of monoamine modulation of a single synapse for regulation of network cycle frequency in the oscillatory pyloric network of the lobster. The pacemaker kernel of the pyloric network receives only one chemical synaptic feedback, an inhibitory synapse from the lateral pyloric (LP) neuron to the pyloric dilator (PD) neurons, which can limit cycle frequency. We measured the effects of dopamine (DA), octopamine (Oct), and serotonin (5HT) on the strength of the LPâPD synapse and the ability of the modified synapse to regulate pyloric cycle frequency. DA and Oct strengthened, whereas 5HT weakened, LPâPD inhibition. Surprisingly, the DA-strengthened LPâPD synapse lost its ability to slow the pyloric oscillations, whereas the 5HT-weakened LPâPD synapse gained a greater influence on the oscillations. These results are explained by monoamine modulation of factors that determine the firing phase of the LP neuron in each cycle. DA acts via multiple mechanisms to phase-advance the LP neuron into the pacemaker's refractory period, where the strengthened synapse has little effect. In contrast, 5HT phase-delays LP activity into a region of greater pacemaker sensitivity to LP synaptic input. Only Oct enhanced LP regulation of cycle period simply by enhancing LPâPD synaptic strength. These results show that modulation of the strength and timing of a synaptic input can differentially affect the synapse's efficacy in the network.
Subject(s)
Motor Neurons/physiology , Nerve Net/physiology , Palinuridae/physiology , Synapses/physiology , Animals , Dopamine/pharmacology , Models, Animal , Motor Neurons/drug effects , Nerve Net/drug effects , Octopamine/pharmacology , Pylorus/innervation , Serotonin/pharmacology , Synapses/drug effects , Time FactorsABSTRACT
The phasing of neuronal activity in a rhythmic motor network is determined by a neuron's intrinsic firing properties and synaptic inputs; these could vary in their relative importance under different modulatory conditions. In the lobster pyloric network, the firing of eight follower pyloric (PY) neurons is shaped by their intrinsic rebound after pacemaker inhibition and by synaptic input from the lateral pyloric (LP) neuron, which inhibits all PY neurons and is electrically coupled to a subset of them. Under control conditions, LP inhibition is weak and has little influence on PY firing. We examined modulation that could theoretically enhance the LP's synaptic contribution to PY firing. We measured the effects of dopamine (DA) on LP-->PY synapses, driving the LP neuron with trains of realistic waveforms constructed from prerecorded control and DA LP oscillations, which differed in shape and duration. Under control conditions, chemical inhibition underwent severe depression and disappeared; in the mixed synapses, electrical coupling dominated. Switching between control and DA LP waveforms (with or without DA present) caused only subtle changes in synaptic transmission. DA markedly enhanced synaptic inhibition, reduced synaptic depression and weakened electrical coupling, reversing the sign of the mixed synapses. Despite this, removal of the LP from the intact network still had only weak effects on PY firing. DA also enhances PY intrinsic rebound properties, which still control the onset of PY firing. Thus in a rhythmic network, the functional importance of synaptic modulation can only be understood in the context of parallel modulation of intrinsic properties.
