**3. AVP vs. OT in terminals and HNS cell bodies**

#### **3.1 Differences in VGCC**

There are subtle differences between the two types of nerve terminals concerning the distribution of the distinct types of VGCCs. The AVP terminals show the L-, N-, and P/Q types of VGCCs, while the OT terminals have the L-, N-, and R types [13]. In contrast, the [Ca2+] responses induced by high K+ (50 mM) involve all Ca2+-channel subtypes in both AVP and OT somata [28]. Electrophysiological studies on the Ca2+ channels in the NH nerve terminals have shown that specific types (Q vs. R) of Ca2+ channels are uniquely important in AVP versus OT secretion (**Figure 1**).

#### **3.2 Primed release of OT**

Mechanisms involved in neurosecretion from the nerve terminals of the AVP- and OT-containing neurons of the HNS are different between this compartment and their somatodendritic region. OT has positive and AVP has various (positive, negative, or no effect) feedback on their release from somata and dendrites, but not from NHTs. Instead, voltage is the primary regulator in terminals. Both compartments utilize intracellular release of Ca2+ to regulate the release of OT but not AVP, which appears regulated primarily by Ca2+ entry through VGCCs. However, MCN dendrites utilize IP3Rs in ER, while NHTs utilize RyRs in NSGs to regulate OT release. Nevertheless, the trafficking of NSGs is the main mechanism for the facilitation of release in both compartments [13, 25, 29]. SNARE-mediated exocytosis is also different in somatodendritic versus NHTs. Thus, these HNS compartments are different in their regulatory mechanisms for neurosecretion. Since OT and AVP are also found in CNS axons and terminals, future experiments are required to determine if differences in the central release (see **Figure 2**) of these peptides compared to the NHTs or somatodendritic regions will have subsequent consequences on their behavioral effects.
