An aggression-specific cell type in the anterior hypothalamus of finches

Abstract

The anterior hypothalamus (AH) is a major integrator of neural processes related to aggression and defense, but cell types in the AH that selectively promote aggression are unknown. We here show that aggression is promoted in a very selective and potent manner by dorsal AH neurons that produce vasoactive intestinal polypeptide (VIP). Fos activity in a territorial finch, the violet-eared waxbill (Estrildidae: Uraeginthus granatina) is positively related to aggression in the dorsal AH, overlapping a population of VIP-producing neurons. VIP is known to promote territorial aggression in songbirds, and thus we used antisense oligonucleotides to selectively block AH VIP production in male and female waxbills. This manipulation virtually abolishes aggression, reducing the median number of displacements in a 3-min resident-intruder test from 38 in control subjects to 0 in antisense subjects. Notably, most antisense and control waxbills exhibit an agonistic response such as a threat or agonistic call within 2 s of intrusion. Thus, antisense subjects clearly classify intruders as offensive, but fail to attack. Other social and anxiety-like behaviors are not affected and VIP cell numbers correlate positively with aggression, suggesting that these cells selectively titrate aggression. Additional experiments in the gregarious zebra finch (Estrildidae: Taeniopygia guttata) underscore this functional specificity. Colony-housed finches exhibit significant reductions in aggression (primarily nest defense) following AH VIP knockdown, but no effects are observed for social preferences, pair bonding, courtship, maintenance behaviors, or anxiety-like behaviors. To our knowledge, these findings represent a unique identification of an aggression-specific cell type in the brain.

Fig. 1.

Histochemically distinct components of the AH exhibit differential responses to agonistic encounters. (A) Fos-ir cell numbers in the AH are significantly increased in subordinate (Sub) but not dominant (Dom) male waxbills relative to control subjects (Con); n = 6 per group. Different letters above the bars denote significant pairwise differences (P < 0.05). (B and C) Fos activation in the dorsal AH (AHd) of dominant birds correlates positively with the number of aggressive displacements given (r² = 0.752, P = 0.02; B), whereas Fos activation in the ventral AH (AHv) of subordinate birds correlates positively with aggression received (r² = 0.704, P = 0.04; C). (D–F) VIP elements in the septohypothalamic region of the zebra finch (D and E) and violet-eared waxbill (F; asterisk shows the injector tract in a scrambled oligonucleotide subject). The dorsal AH region is defined by VIP mRNA and peptide (E and F). (Scale bars, 200 μm in D and 100 μm in E and F.) AC, anterior commissure; AH, anterior hypothalamus; BSTl; lateral bed nucleus of the stria terminalis; BSTm, medial BST; LS, lateral septum (LSr. rostral LS division; LSc., caudal LS division: d, dorsal; v, ventral; vl, ventrolateral); ME, median eminence; MS, medial septum; MSib, internal band of the MS; ot, optic tract; PVN; paraventricular nucleus; SH, septohippocampal septum; v, ventricle; vaf, ventral amygdalofugal tract. D is modified from ref. .

Fig. 2.

Antisense knockdown of VIP production in the AH potently reduces territorial aggression in male and female violet-eared waxbills. (A and B) VIP antisense infusions immediately dorsal to the AH abolish aggressive displacements in most violet-eared waxbills, as measured in a 3-min resident–intruder test (A) and significantly increase the latency to displace the intruder (B). (C) Antisense infusions have no affect on short-latency appraisals of valence, as both antisense and control subjects exhibit an agonistic response (threat, agonistic call, or displacement) very rapidly. **P = 0.01. n = 12 antisense subjects (6 female, 6 male); 9 scrambled subjects (5 female, 4 male).

Fig. 3.

Antisense knockdown of VIP production in the AH reduces aggression in male zebra finches housed in a colony environment. Data shown were collected after 1 d (30 h) of housing in a mixed-sex colony cage, when most males have paired and are defending nest sites. On the basis of behavior in prescreenings, males were housed in low-aggression (blue) or high-aggression (orange) colony cages. *P = 0.02, main effect of treatment; n = 6 per treatment.