NEUR 303 module 2 revision - hormone inputs

Why can estradiol act directly on the brain?

Estradiol is a lipophilic steroid hormone, so it can passively diffuse across the blood–brain barrier.

What brain region is a major site of estradiol action for maternal behaviour?

The medial preoptic area (MPOA) of the hypothalamus.

Which estrogen receptor is most important for maternal behaviour in the MPOA?

Esr1 (ERα).

Approximately what proportion of MPOA cells express Esr1?

About one-third (~1/3).

What maternal behaviours does estradiol mainly support?

Pup-directed caregiving and maternal motivation (pup approach/retrieval).

Which reward-related pathway does estradiol help activate for maternal motivation?

MPOA → VTA → nucleus accumbens (NAc).

How do we know estradiol can induce maternal behaviour?

Classic experiments showed estradiol administration can induce maternal behaviour in female rats.

What experiment showed Esr1 in the MPOA is required for maternal behaviour?

siRNA knockdown of Esr1 in the MPOA impaired maternal behaviour in lactating mice

What chemogenetic evidence supports the importance of Esr1 MPOA neurons in maternal care?

Inhibiting Esr1 MPOA neurons using inhibitory DREADD (hM4Di) impaired pup retrieval.

What optogenetic evidence shows MPOA Esr1 neurons can drive maternal behaviour?

Optogenetic activation of Esr1 MPOA→VTA neurons induced maternal behaviour in virgin females.

What neurotransmitter release is increased when Esr1 MPOA→VTA neurons are stimulated?

Dopamine release in the nucleus accumbens (NAc).

Why is dopamine release in the NAc important for maternal behaviour?

It strengthens reward/motivation signals that promote pup approach and caregiving.

Why can progesterone act directly on the brain?

Progesterone is lipophilic and can cross the blood–brain barrier.

What is the main progesterone receptor in the maternal circuit?

Pgr

Where does progesterone mainly act to influence maternal behaviour?

The MPOA (especially on hormone-sensitive neurons).

How is progesterone receptor expression related to estrogen receptor expression in the MPOA?

About half of Esr1-expressing MPOA cells also express Pgr.

What is progesterone’s key role in preparing the maternal circuit during pregnancy?

It helps remodel MPOA neurons to support maternal behaviour at parturition.

Which key maternal neuron type is influenced by progesterone in late pregnancy?

MPOA galanin neurons.

What structural change does progesterone promote in MPOA galanin neurons?

Increased dendritic spine density.

Why is increased spine density important for maternal behaviour?

It likely increases excitatory (glutamatergic) synaptic input, priming neurons for activation.

What evidence suggests estrogen and progesterone receptors in the MPOA are necessary for pup retrieval?

Deleting estrogen or progesterone receptors from MPOA cells disrupted pup retrieval in virgin and pregnant mice.

How do estradiol and progesterone interact in preparing maternal behaviour?

They act synergistically to prime MPOA neurons (especially galanin neurons) for maternal responses.

Why is prolactin different from estradiol and progesterone in terms of brain entry?

Prolactin is a large peptide hormone (~23 kDa) and cannot freely cross the BBB.

How does prolactin enter the brain to influence maternal behaviour?

Through a receptor-mediated transport system across the BBB (increased during lactation).

What receptor do prolactin and other lactogens act through?

The prolactin receptor (Prlr).

What intracellular pathway is activated by the long form of the prolactin receptor?

The JAK/STAT signalling pathway.

What molecular marker is used to identify prolactin receptor activation?

Phosphorylated STAT5 (pSTAT5).

What evidence shows prolactin receptor signalling is increased during lactation?

Very high pSTAT5 labelling in the MPOA of lactating mice.

What classic experimental evidence supports prolactin’s role in maternal behaviour?

Repeated prolactin administration to virgin rats accelerated maternal behaviour during pup exposure.

What experiment showed prolactin acts directly in the MPOA to induce maternal behaviour?

Direct infusion of prolactin into the MPOA induced maternal behaviour in virgin rats.

What is the strongest evidence that prolactin action in the MPOA is essential for maternal behaviour?

Cre-lox deletion of prolactin receptors specifically in MPOA neurons caused pup death by day 2 due to maternal abandonment.

How do we know the pups died due to maternal behavioural failure, not pup health?

Foster mothers successfully raised the pups, showing the pups were healthy.

What does prolactin mainly contribute to in maternal behaviour (functionally)?

Long-term maternal adaptations, motivation, and sustained caregiving during lactation.

What cell-type evidence suggests prolactin supports maternal motivation under stress?

Deleting prolactin receptors in MPOA GABA neurons caused deficits mainly in stressful (novel cage) maternal tasks.

Why is prolactin considered critical for offspring survival?

Without prolactin receptor signalling in MPOA neurons, maternal care fails and pups die early in lactation.