Basu Sumela, Waghade Akash, Parveen Roshni, Kushwaha Ayushi, Mitra Saptarsi, Kokare Dadasaheb M, Singru Praful S
School of Biological Sciences, National Institute of Science Education and Research (NISER)-Bhubaneswar, India.
Homi Bhabha National Institute (HBNI), Mumbai, India.
J Neurosci. 2025 Mar 14;45(17). doi: 10.1523/JNEUROSCI.2140-24.2025.
Compared to males, aggression is less frequently noticed in females. Fierce maternal-aggression to thwart the attack/threat of male-conspecific/intruder is transiently expressed as she defends her pups. The odor cues emanated by the intruder provoke aggressive behavior by robustly activating the ventral-premammillary nucleus (PMv) in the hypothalamic-attack area (HAA). But, how PMv activation triggers aggression is unclear. In view of neuropeptide CART's potential to reconfigure neural circuits for behavioral demands, occurrence throughout aggression-circuitry, and abundance particularly in PMv, we test the role of PMv in maternal and inter-male aggression in the rats. Males/dams actively attacked the intruder; virgin-females did not. The dams/males without intruder showed isolated cFos-cells in PMv, but intruder's presence triggered cFos-activation in different PMv-subdivisions in dams/males. Compared to dams without intruder, confrontation with intruder robustly activated PMv-neurons, augmented CART-ir in ventral-PMv and -mRNA in PMv-containing tissues in dams. Conversely, in males, intruder's presence activated lateral-PMv CART neurons, but CART-levels remained unaltered. Intra-PMv CART-siRNA administration suppressed maternal-aggression but male-aggression was unaffected. Since PMv is strongly connected with ventrolateral-ventromedial hypothalamus (VMHvl) and medial-preoptic nucleus (MPN), we test whether CART-signalling to these nuclei triggers maternal-aggression. While VMHvl showed stronger CARTergic-axonal input than MPN, immunoneutralization of CART in VMHvl but not MPN, blocked maternal-aggression. CART may drive the circuit beyond HAA since VMHvl neurons contacted by CART-axons project to periaqueductal-gray. We identify engagement of vPMv and lPMv during maternal and inter-male aggression, respectively, and CART as a key mediator in PMv-VMHvl-pathway to express maternal-aggression in rats. Pregnant/lactating rat transiently become fiercely aggressive to protect her pups when challenged by an intruder. The neural mechanism underlying this transitory expression of aggressive behavior is not clear. We identify the role of neuropeptide CART-containing neurons in the hypothalamic premammillary nucleus (PMv) in dams that gives her the behavioral flexibility to display maternal-aggression. A subset of PMv neurons in dams shows dramatic activation when provoked by an intruder while silencing of these neurons suppressed maternal- but not male-male aggression. Further, CART signals the ventrolateral part of the ventromedial hypothalamus to trigger aggression in dams. The study shows CART as a novel messenger in aggression circuitry and PMv a key regulator of maternal-aggression.
与雄性相比，雌性的攻击性较少被注意到。当雌性保护幼崽时，会短暂地表现出强烈的母性攻击性，以挫败雄性同种个体或入侵者的攻击/威胁。入侵者散发的气味线索通过强烈激活下丘脑攻击区域（HAA）中的腹侧乳头前核（PMv）来激发攻击行为。但是，PMv激活如何触发攻击尚不清楚。鉴于神经肽CART具有根据行为需求重新配置神经回路的潜力，其在整个攻击回路中均有出现，且在PMv中含量尤其丰富，我们测试了PMv在大鼠母性攻击和雄性间攻击中的作用。雄性/母鼠会主动攻击入侵者；未生育的雌性则不会。没有入侵者时，母鼠/雄鼠的PMv中显示出孤立的cFos细胞，但入侵者的出现会触发母鼠/雄鼠不同PMv亚区的cFos激活。与没有入侵者的母鼠相比，与入侵者对峙会强烈激活PMv神经元，增加母鼠腹侧PMv中的CART免疫反应性以及含PMv组织中的CART mRNA。相反，在雄性中，入侵者的出现会激活外侧PMv的CART神经元，但CART水平保持不变。向PMv内注射CART-siRNA可抑制母性攻击，但对雄性攻击没有影响。由于PMv与下丘脑腹外侧腹内侧核（VMHvl）和视前内侧核（MPN）有很强的联系，我们测试了CART向这些核的信号传递是否会触发母性攻击。虽然VMHvl显示出比MPN更强的CART能轴突输入，但VMHvl而非MPN中CART的免疫中和会阻断母性攻击。CART可能驱动了超出HAA的回路，因为与CART轴突接触的VMHvl神经元投射到导水管周围灰质。我们分别确定了在母性攻击和雄性间攻击过程中腹侧PMv和外侧PMv的参与情况，并确定CART是PMv-VMHvl通路中表达大鼠母性攻击的关键介质。怀孕/哺乳的大鼠在受到入侵者挑战时会短暂地变得极具攻击性以保护其幼崽。这种攻击行为短暂表达的神经机制尚不清楚。我们确定了下丘脑乳头前核（PMv）中含神经肽CART的神经元在母鼠中的作用，该作用赋予了母鼠表现出母性攻击的行为灵活性。当受到入侵者刺激时，母鼠中一部分PMv神经元会出现显著激活，而沉默这些神经元会抑制母性攻击，但不会抑制雄性间攻击。此外，CART向下丘脑腹内侧核的腹外侧部分发出信号以触发母鼠的攻击。该研究表明CART是攻击回路中的一种新型信使，而PMv是母性攻击的关键调节因子。
