Neurobiology of Maternal Behaviour Author Paul Kenyon Overview Sensory factors in maternal behaviour Olfaction Auditory cues Perioral sensation and retrieving Perioral sensation and suckling A model of sensory regulation of maternal behaviour in the female rat Neural factors in maternal behaviour The medial preoptic area Numan and Carlson's model of hormone effects on maternal behaviour The ventral tegmental area Testing Stern's and Numan's theories References Online text resources: Supplementary material Further reading    Visit the SALMON Bookshop for recommended books on this topic

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Overview:
New-born rat pups appear helpless little pink bundles of potential behaviour. Don't be fooled, they are already behaving their little heads off! You may think they are "helpless passive recipients of maternal care", but they are from it. They are engaged in an intricate behavioural dance with their parents for survival. New-born pups play an active role in eliciting maternal behaviour from their mothers. In this lecture we will explore some of the factors that control this reciprocal partnership. Rat mothers are attracted by the sight, sound and odour of their pups. Pups utilize perioral sensations to locate and suckle from their mother's nipples.

The lecture concludes with a model put forward by Carlson that suggests how estrogen interacts with brain regions involved in maternal behaviours. You should link this model with the material we covered on hormonal regulation of maternal behaviour

Sensory factors in maternal behaviour

Olfaction

 A virgin female rat does not normally approach a rat pup; in fact when she encounters one, she retreats from the pup as if she was repelled by the pup's odour. However, if virgin rats are continuously exposed to rat pups over several days, they eventually exhibit maternal behaviours and will retrieve pups and adopt the nursing posture even though they do not lactate. This process is called sensitization.

Olfaction plays an important role in inhibiting maternal behaviour in nonpregnant rats.

Mayer & Rosenblatt (1980) confirmed that initial avoidance of pups is based on their odour. They rinsed the olfactory mucosa (lining of the nose) of virgin female rats with zinc sulphate, which temporarily eliminates olfactory sensitivity. Animals that cannot smell are called anosmic , they experience a state called anosmia. Zinc sulphate treatment abolished the virgins' natural aversion to pups, and they started taking care of them. Thus, sensitization involves overcoming a natural aversion to the odour of pups.

This diagram shows the initiation of maternal behaviour by nonpregnant (virgin) females following Hysterectomy+Ovariectomy (HO) + estrogen treatment and/or olfactory-vomeronasal deafferentation by intranasal zinc sulphate (ZnSO4) which renders the rats anosmic - unable to smell. Rats were hysterectomized and ovariectomized in order to remove natural fluctuating sources of estrogen and progesterone from the body. Virgin female rats were exposed to groups of 4 pups, 3-8 days of age, during the dark phase of the daily 12:12 hr cycle. Females were considered to have initiated maternal behaviour when they retrieved all test pups during two tests one day apart. Treatment designations: HO-EB100,ZnSO4 = hysterectomy + ovariectomy + 100 mg/kg estradiol benzoate injections + intranasal injection of ZnSO4 HO-EB200,ZnSO4 = hysterectomy + ovariectomy + 200 mg/kg estradiol benzoate injections + intranasal injection of ZnSO4 SHAM-OIL = sham hysterectomy + ovariectomy + oil injection ZnSO4 = intranasal injection of ZnSO4 Air = sham injection of air

Auditory cues and maternal behaviour

Rat pups emit ultrasonic calls (sounds that we cannot hear) that can be detected via a "bat detector". If the pup gets cold - because it is outside the nest - it emits a characteristic call that allows the mother to locate the pup so that it can be picked up and taken back to the nest. But an experiment by Smotherman et al (1974) shows that rat mothers only respond to this auditory cue if it is accompanied by an olfactory cue from the pup.

Smotherman's experiment involved giving mothers who had delivered a litter of pups, a series of tests in the apparatus shown here. Stimuli which differed in their auditory and olfactory qualities were placed in each choice arm of the apparatus:

• a handled pup which smells and emits distress calls
• a chilled pup which smells, but does not emit auditory stimuli
• a tape loop of pup's ultrasonic distress calls

The stimuli were hidden behind a screen at the end of each arm to prevent the female basing her choice on visual cues.

This diagram shows the mothers' preferences when faced with each stimulus combination:

• handled pups were preferred to chilled pups
• handled pups were preferred to the tape of pup distress calls
• the tape loop was preferred to the chilled pup

mothers showed no preference for:

• the tape loop over an empty arm, or
• a chilled pup over the empty arm

These results suggest that the smell of pups outside the nest is required before mothers use auditory cues to locate their displaced pups and retrieve them to the nest.

In other words, mothers only respond to the auditory cue when it occurs in the presence of pup odour.

Perioral sensation and retrieving

Tactile (touch) cues are very important in controlling a number of rat behaviours.

The photograph shows the location of the vibrissae (whiskers) in adult rats and pups.

You can see from this photograph just how delicate the mother's retrieving behaviour must be in order to prevent damaging the pup's skin.

Sensation from the region around the mouth (the perioral area) can be abolished by injecting a local anaesthetic (e.g. lidocaine) into the mystacial (vibrissal) pads which blocks conduction along the infraorbital nerve which conducts tactile information from the whiskers to the brain).

Rats lacking perioral sensation are called anaptic, they are said to be in a state of anapsis.

This procedure is done under general anaesthetic in order to minimize any distress experienced by the animal due to injection.
This diagram shows the results of an experiment (Kenyon et al 1983) that examined the role of perioral sensation in maternal behaviour.

Under general anaesthetic lidocaine or saline was injected into

• either the vibrissal pads
• or the masseter muscles

of lactating female rats.

Injecting lidocaine into the vibrissal pads, reduced the number of pups that were retrieved in tests given 30 and 60 minutes after injection. As the effects of the local anaesthetic wore off (120 and 180 minute tests) retrieving behaviour recovered.

Injecting lidocaine into the masseter muscles had no effect on the mothers' ability to retrieve her pups. Thus the effect of lidocaine is site-specific which indicates that lidocaine is not having a general debilitating effect on the animal's behaviour.

Perioral sensation and suckling

This diagram (Kenyon et al 1982) shows the percentage of pups attaching to the nipples of an anaesthetized dam after injection of saline or lidocaine into the vibrissal pads, or into the region of the masseter muscle. The results indicate that injecting lidocaine into the pups' vibrissal pads disrupts suckling injecting saline into this area does not affect pups' ability to attach to nipples The effect of lidocaine is site-specific. Injecting local anaesthetic into the pups' masseter muscles does not prevent pups from attaching to their mother's nipples. Point to ponder What further control experience would you run to ensure these results were caused by a lack of perioral sensation (anapsis)?

In this experiment Blass et al (1977) found that removing the odour from the nipples of lactating female rats made them so unattractive that hardly any rat pups were prepared to attach to them. However pups were prepared to suckle if the nipples were painted with an extract from the original washings. This result was interpreted as indicating that pups used an olfactory (smell) cue to locate their mother's nipples. Point to ponder: Washing the nipples may have altered their texture (as well as smell). How would you test the possibility that a change in nipple texture, rather than removing nipple odour, disrupted suckling?

A model of sensory regulation of maternal behaviour in the female rat.

Stern (1989) suggests that there is a complex and integrated 'dance' between rats pups and their mothers that 'choreograph' maternal behaviours.

When pups are outside the nest the mother responds to distal cues - the sight, sound and smell of displaced pups. We have seen how the smell of pups is required to motivate the mother to leave her nest, whilst she locates the pups based on their ultrasonic calls.

When the mother comes into contact with her pups proximal cues stimulate her to nuzzle, lick and hover over her pups. We have seen that abolishing perioral sensation by injecting lidocaine into the mother's snout abolishes retrieving behaviour.

Pups also play a more active role in influencing mothers' behaviour. We have seen that abolishing perioral sensation disrupts pups' ability to attach to their mother's nipples. But in addition, when pups nuzzle their mother's ventral surface (belly) the mother becomes still, her back arches and she crouches over her pups. Stern calls this behaviour kyphosis and clearly it would aid pups find and attach to nipples.

Stern (1989) reviews a number of experiments which show that kyphosis is disrupted

• if pups are injected with lidocaine in their mystacial pads so that they do not root their mother's ventral surface, or
• the mother's ventral surface is anaesthetized so that they cannot feel their pups rooting

This table summarizes the parts played by sensory factors in the interactions between mother rats and their offspring.

Mother	Pups
Distal cues stimulate mother to seek contact with pups	Pups provide distal cues: sight, sound, and smell for the mother
Perioral contact with her pups stimulates the mother to nuzzle, lick and hover over pups	The mother makes perioral contact with pups
Pups making ventral contact with the mother stimulates her to adopt the crouching posture	The pups nuzzle the mother's ventral surface. The crouching posture facilitates the pups' suckling behaviour

Neural factors in maternal behaviour
The medial preoptic area

So far, this lecture has focussed on the role of sensory factors in maternal behaviour. For example, you now appreciate that anosmia facilitates the onset of maternal behaviour, and that intact perioral sensation is a prerequisite for retrieval.

In a previous lecture we saw that

• estrogen rises, and progesterone declines, at the end of a normal pregnancy
• an increase in estrogen stimulates maternal behavior when progesterone levels are low after hysterectomy during pregnancy.

Quite clearly the brain must play an important role in mediating the effects of hormones and sensory factors on maternal behaviour.

Where in the brain does this integration take place? One possibility is that estrogen overcomes a rat's natural aversion to the smell of pups, and that this process occurs in an area of the hypothalamus called the medial preoptic area (MPOA).

There are several reasons for focussing on the MPOA:

• MPOA lesions profoundly disrupt retrieving and suckling behaviours
• there are nerve pathways which convey olfactory information from the olfactory bulbs to the MPOA
• cells in the MPOA bind estrogen

Numan et al (1977) investigated the possibility that the MPOA was the area of the brain where estrogen influences maternal behaviour. In this experiment all the subjects were virgin rats who were mated and on Day 16 of pregnancy they were all hysterectomized and ovariectomized. You will recall from a previous lecture that maternal behaviour is facilitated by the rise in estrogen which occurs shortly after pregnant rats are hysterectomised on Day 16 of pregnancy. But this facilitation of maternal behaviour does not occur if the rats are also ovariectomised. Ovariectomy removes a natural source of estrogen. Thus the 16 Day hysterectomised-ovariectomized pregnant rat can be used to study the role of estrogen in the onset of maternal behaviour.

Numan et al (1977) studied five independent groups of rats that had estrogen injections in various areas on Day 16 of pregnancy:

• EB-MPOA estrogen was implanted into the medial preoptic area
• EB-VMH estrogen was implanted into the ventromedial hypothalamus
• EB-MB estrogen was implanted into the mammillary bodies
• EB-SC estrogen was injected under the rats' skin (subcutaneous)
• Chol-MPOA cholesterol was implanted into the medial preoptic area

Cholesterol was used as a placebo control. Cholesterol is a steroid which has a similar chemical structure to estradiol. Implanting estrogen into the VMH, MB and subcutaneously was done to check that any effects produced by MPOA implants were site-specific.

The diagram below shows the cumulative percentage of 16 day pregnant hysterectomised (H) and ovariectomised (O) female rats showing maternal behaviour over the five day test period (Numan et al 1977). Compared to the other groups, rats with estradiol implanted into the MPOA show rapid onset of maternal behaviours when they are presented with foster pups. You can use this diagram to satisfy yourself that the MPOA is the most effective site for implanting estrogen to facilitate maternal behaviour.

Abbreviations: MB - mammillary bodies VMH- ventromedial hypothalamus MPOA - medial preoptic area	EB - estradiol benzoate sub cut - subcutaneous (under the skin) Chol - cholesterol

Carlson and Numan's model of hormone effects on maternal behaviour
This diagram that shows how various interconnected areas of the brain could be involved in the rat's reaction to pup odour.

Olfactory information about the pup is received by the olfactory bulbs, then passed to the medial nuclei of the amygdala via the lateral olfactory tract.

The amygdala is thought to exert an inhibitory influence over the medial preoptic area (MPOA) which is transmitted down the stria terminalis

The output of the MPOA passes through the ventral tegmental area to terminate in areas of the brain involved in motor functions.

Carlson (2001) reviews the evidence that supports this model.

Here are the components of Numan and Carlson's model highlighted on a sagittal section of the rat brain. Lesioning: the lateral olfactory tract or the stria terminalis facilitates the onset of maternal behaviour, presumably by blocking the transmission of aversive olfactory information Lesioning: the MPOA or the ventral tegmental area disrupts maternal behaviour Medial amygdala inhibition of the MPOA can be overcome by injecting estradiol directly into the MPOA.

The ventral tegmental area (VTA)

In the diagram of Carlson's model the MPOA is depicted as an area of the brain which receives hormonal (estrogen) and sensory (odour) information, integrates this information, and sends instructions to motor areas of the brain to perform maternal behaviour. The nerves that carry these instructions pass through the VTA. Consequently VTA lesions disrupt behaviour because they destroy this pathway which is responsible for the initiation of motor activity.

But Stern (1989) has argued that the effects of VTA lesions can be explained in a completely different way. She points out that the nerves carrying sensory information from the rat's snout run across the top of VTA. This pathway is called the trigeminal sensory pathway. Stern argues that VTA lesions would also damage this sensory pathway. She argues that damage to this pathway is responsible for the effects seen in rats with VTA lesions.

Earlier we studied an experiment in which retrieving behaviour was abolished after lidocaine was injected into the snout to block conduction in the trigeminal nerve. Stern suggests that sensory information travelling through the trigeminal pathway may reach the MPOA. She argues that the reason MPOA land VTA lesions disrupt maternal behaviour is because the mother rat is unable to process the sensory tactile information from pups that controls her behaviour.

In a nutshell:

• Stern argues that VTA lesions abolish the passage of sensory information from the rat's snout to the MPOA
• Numan argues that VTA lesions abolish the passage of information from the MPOA to motor control areas of the brain

We have already mentioned that electrical lesions which destroy the VTA - and any nerve fibres passing through the VTA - severely disrupt maternal behaviour. This result is predicted by both theories. Furthermore, maternal behaviour is not disrupted if a chemical - that destroys cells in the VTA, but does not interfere with nerve fibres that travel through the VTA - is injected into the VTA. Again this result would be predicted by both theories. You can explore the effects of chemical and electrical lesions and the two theories in the diagram above.

Testing Stern's and Numan's theories

One way of testing Numan and Stern's theories would be to compare the effects outside the VTA on maternal behaviour of lesions :

• according to Numan, a lesion of the pathway between the VTA and motor control areas should disrupt maternal behaviour, but not affect perioral sensation
• according to Stern, lesioning the ascending trigeminal pathway before it reaches the VTA should also disrupt maternal behaviour

Numan and Numan (1991) report that "coronal knife cuts located in the midbrain tegmentum at a point caudal to the VTA severely disrupted maternal behaviour", but perioral tactile sensitivity was not affected by this operation.

These results support their suggestion that a pathway running from the MPOA through the VTA projects to brain areas involved in motor functions.

It is difficult to explain these results in terms of the lesion interfering with perioral sensation, because a test of perioral sensation showed that there was no difference between sham operated and lesioned rats.

One way to test Stern's theory is to cut the infraorbital branch of the trigeminal nerve that carries sensory information from the rat's snout to its brain.

Kenyon et al (1983) cut the infraorbital branch of the trigeminal nerves which transmitting sensory information from the mystacial pads to the brain. The results shown here indicate a profound but short-lasting disruption of maternal behaviour after this operation. In addition perioral tactile sensation was abolished by this operation. Kenyon and Numan's results indicate that maternal behaviour is disrupted by: either, lesioning pathways that carry sensory information to the brain or, cutting nerve pathways that carry instructions to initiate motor actions within the brain

References

• Blass et al (1977). Journal of Comparative and Physiological Psychology, 91, 1248-1260.
• Carlson (2001) Physiology of Behavior, Alyn & Bacon, New York.
• Fleming, Corter, Franks, Surbey, Schneider, and Steiner (1983). Dev. Psychol. 26, 137-143.
• Kaitz (1987). Developmental Psychobiology, 20, 587-591.
• Kenyon, Keeble, Cronin (1982). Developmental Psychobiology, 15, 409-421.
• Kenyon, Cronin and Keeble (1983).Behavioral Neuroscience, 97, 255-269.
• Mayer & Rosenblatt (1980). Journal of Comparative and Physiological Psychology, 94, 1040-1059.
• Numan, Rosenblatt and Komisaruk (1977). Journal of Comparative and Physiological Psychology, 91, 146-164.
• Numan and Numan (1991). Behavioural Neuroscience, 105,1013-1029.
• Smotherman et al (1974). Behavioral Biology, 12, 55-66.
• Stern (1989) In Brush and Levine (Eds). Psychoendocrinology, Academic Press, San Diego, California.
  

Online text resources:

Daly M, Wilson M (1999c) An evolutionary psychological perspective on homicide. In D. Smith & M. Zahn, eds. Homicide Studies: A Sourcebook of Social Research, p. 58-71. Daly M, Wilson M (1998d) The Truth About Cinderella. London: Weidenfeld & Nicolson Publishers. [U.S. edition: Yale University Press 1999] Hagen, EH (1999) The Functions of Postpartum Depression. Evolution and Human Behavior. 20:325-359. A fuller version of this paper is available online Hagen, EH (2000) Are depressed individuals 'going on strike'?. Paper presented at the Human Behavior and Evolution Society Annual Meeting, Amherst, MA 2000.

Supplementary material

There are some impressive sets of vibrissae out there! As you may have realised during the lecture I am very interested in the role played by vibrissae in controlling various aspects of rat behaviour. Here are some sources of further information. It is worth looking at some of these links to get a feel for how study of an apparently esoteric sensory system in the rat may lead to fundamental breakthroughs in our understanding of the relationship between brain and behaviour. Thomas A. Woolsey of Washington University provides an elegant and short explanation of how studying vibrissae can enhance our understanding of the structure, function and development of the central nervous system. Victor Pegado of McMaster University has published a diagram showing that a very large area of rat brain is devoted to processing vibrissal information. His site also contains pictures of the barrel fields in the somatosensory cortex of a rat. One of the reasons people are interested in vibrissae is that it is possible to trace structures running from the vibrissae all the up through the brain to the cortex that are responsible for processing information from each single vibrissae. For example, if a single vibrissae is removed in a very young rat there is a corresponding 'hole' in the somatosensory cortex. Dr. Brad Klein in the Dept. of Biomedical Sciences and Pathobiology at the Virginia-Maryland Regional College of Veterinary Medicine at Virginia Tech is researching the function of the the trigeminal system. Heinz Steiner at The University of Tennessee, Memphis uses the trigeminal system (which transmits vibrissal information) to study neuroplasticity. Barry D. Waterhouse of Temple University uses the vibrissal system in his quest to understand norepinephrine and serotonin regulate the responsiveness of sensory neurons and sensory circuits to synaptic inputs. This paper Rat exploratory behavior following infraorbital deafferentation or selective cerebellar lesions by Michael Lin, Josée Morissette, Mitra J. Hartmann, and James M. Bower reports no significant effect of cutting the trigeminal nerve on exploratory behaviour. Can you think of an explanation for this lack of effect? Moore, Sur and Nelson working at MIT report their study of sensory responses from neurons in rat somatosensory cortex. All you ever wanted to know about Somatic Sensory Cortical Regions of the Agouti