Research On Effects Of Arginine Vasopressin Modulation Of GABAergic Synaptic Transmission To Preoptic Area Neurons In Hypothalamus

Arginine vasopressin(AVP)is an important endogenous mediator in thermoregulation.Previous in vivo studies indicate that AVP plays a tonic negative regulation role in thermoregulation.Moreover,AVP increased the spontaneous firing activity and firing rate thermosensitivity of warm-sensitive neurons while it decreased that in cold-sensitive and temperature-insensitive neurons in preoptic area(POA).Since the preoptic area(POA)of the hypothalamus,containing temperature-sensitive and temperature-insensitive neurons,plays a key role in specific thermoregulatory responses,these results indicate that there exists an association between the AVP-induced tonic negative thermoregulation and AVP-induced change in firing activity of POA neurons.The mechanisms of AVP controlling firing activity of POA neurons,however,remain unclear.Herein,the membrane potential and inhibitory postsynaptic currents(IPSCs)of temperature-sensitive and temperature-insensitive neurons in POA slices were recorded using whole-cell patch clamping during bath applications of AVP or V1 a vasopressin receptor antagonist.By monitoring neuron's changes of resting potential and membrane potential thermosensitivity before and during AVP or V1 a vasopressin receptor antagonist perfusion,we found that AVP increased the change of resting potential in 50% temperature-insensitive neurons and reduced it in the others.These changes are due to the AVP enhancing the thermosensitivity of membrane potential in nearly 50% temperature-insensitive neurons.For temperature-sensitive neurons,however,AVP changed the resting potential and membrane potential thermosensitivity,but there were no resulting differences between the different neuronal types.In all neurons,there was no correlation between firing rate thermosensitivity and change in membrane potential before and during AVP or V1 a vasopressin receptor antagonist perfusion.Meanwhile there was no correlation between firing thermosensitivity and membrane potential thermosensitivity in all neurons when experimental perfusion.By monitoring changes in GABAergic transmission during AVP treatment,we showed that AVP decreased the amplitudes and frequencies of spontaneous IPSCs in most warm-sensitive neurons and in some temperature-insensitive neurons but increased these parameters in other temperature-insensitive neurons.The IPSC amplitude was reduced for only cold-sensitive neurons.Immunohistochemistry,RT-PCR and Western blot analyses further confirmed the POA expression of V1 a receptors and GABAA receptors,including the subunits ?1,?2,?3,?2,?3 and ?2.The effects of AVP on IPSCs in temperature-sensitive and temperature-insensitive neurons were dependent on G proteins,intracellular Ca2+,PKC and Ca MKII.AVP-changed in the kinetic parameters(decay time,10%-90% rise time,half width)was associated with the phosphorylation of ?2 by PKC and Ca MKII.Together,this studies suggesting that AVP-induced the changes in firing activity and firing rate thermosensitvity of POA neurons is controlled,not by resting potentials,but rather by transient potentials that are rapid changes in membrane potential between successive action potentials.AVP,acting via V1 a receptors but not V1 b receptors,differentially modulates GABAergic synaptic transmission and fine-tunes the firing activities of temperature-sensitive and temperature-insensitive neurons in the rat POA.