Division of Developmental Psychobiology - NYSPI @ Columbia University
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NIMH TRAINING GRANT

Laboratory of newborn mother-directed behaviors

 

 

 

H. Jonathan Polan, M.D.
Phone: 543 5022, Room: 4915

Lab members:
Michiko Okamoto, PhD., Vanessa Winiger

 

A young mammal's ability to gain closeness and contact with its mother is required for its survival and is a fundamental component of its attachment relationship to her. Disturbances of attachment in human infants are found in autism, early deprivation, and failure-to-thrive; the consequences of attachment disturbances are thought to include predispositions to anxiety and depressive disorders in later life. To understand these disturbances and potentially remediate them, we have been investigating the determinants of the earliest attachment behaviors in the rat.

We have identified the newborn rats' repertoire of maternally-directed orienting behaviors (MDOBs): locomotion, torso flexion, rotation to the supine orientation, and snout probing, accompanied by audible vocalizations (“barking”). At birth, the behaviors are performed at high rates, but are only weakly responsive to specific features of the mother. Differential responsiveness to features of the mother's body, such as warmth, fur texture, and odor, is acquired over the first two postnatal days, concurrent with the emergence of an organized structure among these behaviors. Differential responding to maternal features is, in part, dependent on the first day's experience with the mother, suggesting that learning plays a role in its development. In addition, at postnatal day 2, a period of maternal deprivation induces a marked heightening of MDOBs, suggesting the emergence of an early motivation-like system.

Most recently we have documented exactly analogous MDOBs in newborn mice. We studied the consequences in the mouse of knocking out a gene for glutaminase, the enzyme that is responsible for making one of the brain's excitatory neurotransmitters, glutamate. Newborns that have no copies of this glutaminase gene die within 48 hours after birth lacking milk in their stomachs, whereas their siblings with only one copy of the glutaminase gene (heterozygotes) appear normal and grow to maturity just as do siblings with both normal copies of the gene. We found that the full knockout infants have dramatically reduced MDOBs even though they are no less active than their siblings compared to their normal siblings. The heterozygotes' have frequencies of MDOBs intermediate between the knockouts and the normals. Evidently the heterozygotes' MDOBs are sufficient to asssure survival and grossly normal development. This is the first instance of a "dose response" relationship demonstrated for a neurobiologically important gene and MDOBs.

At the same time, we are investigating animal models of schizophrenia in transgenic mice with mutations engineered to affect neurotransmitters, such as dopamine, thought to be involved in the pathophysiology of this severe psychiatric illness. This work is conducted with our collaborators in the University's Center for Neurobiology and Behavior.


Relevant Publications:

Masson, J., Darmon, M., Conjard, A., Chuhma, N., Ropert, N., Thoby-Brisson, M., Foutz, A.S., Parrot, S., Miller, G.M., Jorisch, R., Polan, H.J., Hamon, M., Hen, R., & Rayport, S. (2006) Mice lacking brain/kidney phosphate-activated glutaminase (GLS1) have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth. Journal of Neuroscience, 26:4660-4671.

Kellendonk, C., Simpson, E., Polan, H.J., Malleret, G., Vronskaya, S., Winiger, V., Moore, H. & Kandel, E.R. (2006) Transient and Selective Overexpression of Dopamine D2 Receptors in the Striatum Causes Persistent Abnormalities in Prefrontal Cortex Functioning. Neuron, 49: 603-615.

Etkin, A., Pittenger, C., Polan, H.J. & Kandel, E. R. (2005) Toward a Neurobiology of Psychotherapy: Basic Science and Clinical Applications. J Neuropsychiatry Clin Neurosci, 17:145-158.

Polan, H.J. (2005) Probing the origins of attachment: Guidance and differentiation of the first mother-directed behaviors. Developmental Psychobiology, 47:278-287.

Sullivan, RM, Landers, MS, Flemming, J, Vaught, C, Young, TA, and Polan, HJ. 2003. Characterizing the functional significance of the neonatal rat vibrissae prior to the onset of whisking. Somatosensory and Motor Research, 20:157-162.

Sullivan, RM, Landers, MS, Flemming, J, Vaught, C, Young, TA, and Polan, H.J. (2003) Characterizing the functional significance of the neonatal rat vibrissae prior to the onset of whisking. Somatosensory and Motor Research, 20:157-162.

Polan, H.J., Eljuga, L., Sacks, T., & Hofer, M.A. (2002) Deprivation regulates nipple grasp by P2-3 rat pups in a naturalistic paradigm. Developmental Psychobiology, 41:89.

Polan, H.J. & Hofer, M.A. (1999) Maternally-directed orienting behaviors of newborn rats. Developmental Psychobiology, 34:269-279.

Polan, H.J. & Hofer, M.A. (1999) Psychobiological origins of separation and attachment responses. In Cassidy, J. & Shaver, P. R. (Eds.), Handbook of Attachment: Current Theory and Research. Chapt. 8, pp. 162-180. Guilford:New York.

Polan, H.J.
& Hofer, M.A. (1998) Olfactory preference for mother over home nest shavings by newborn rats. Developmental Psychobiology, 33:5-20.