Figure 6.

Schematic representation of hypothetical action mechanisms of cannabinoids on IC neurons that exhibit SSA. (I.A) An inhibitory input (probably GABAergic, green) contacting a postsynaptic IC neuron (purple). Basal activity is shown as action potentials (yellow) in the postsynaptic neuron. GABA release affects the activity of the neuron by acting on postsynaptic receptors. (I.B) Agonist drugs that activate presynaptic CB1R on the inhibitory terminal lead to an increase in the firing rate of the postsynaptic neuron due to a decrease in the GABA release. Both agonists produce an increase of the firing rate in response to the standard frequency; thus, the CSI of the postsynaptic SSA IC neuron decreases. We cannot rule out the possible involvement of other neuromodulatory substances in the final result. (I.C) Injection of the CB1R antagonist AM251 producs a blockade of the basal ECB and/or the constitutive activity of the receptors, hence GABA is released, decreasing the firing rate for standard stimuli that results in a CSI increase. (II) If CBRs are located in the postsynaptic neurons, their activation should promote both an inhibition of adenylyl cyclase, and a change in the open probability of ionic channels (K⁺ and Ca²⁺) that would lead to a decrease in neuronal activity.