The Haber lab focuses on the neural network that underlies incentive learning and decision-making that leads to the development of action plans. The cortico-basal ganglia-thalamic system is central to this network and comprises a diverse group of structures involved in reward and motivation, cognition, and motor control.  Pathology of this network is implicated in several mental health disorders including drug addition, obsessive-compulsive disorder, and schizophrenia.

Experiments in Dr. Haber's laboratory address the hypothesis that the cortico-basal ganglia connections modulate both functionally discrete cortical pathways, but also are critical for integrating information across functional domains.  These complex neuronal networks work in concert with the cortex to moderate behavioral changes and provides the anatomical substrate for plasticity during learning.  Specific questions include: 1) What is the organization of cortical and thalamic connections that mediate information flow through the basal ganglia?  2) How are pathways involved in reward processing and cognition integrated into the basal ganglia pathways of action? 3) What is the interface between the descending cortico-basal ganglia system and the midbrain dopamine system?  4) Are there postnatal developmental changes of connections, cell types, transmitter systems, and receptors that are consistent with the high level of plasticity during early learning?

In order to understand the complex interconnections between these brain regions and their the associated neurotransmitters and receptors, we have developed 3-D models of structures, pathways, and terminal fields along with transmitter and receptor systems, with a particular focus on cortical, striatal, dopamine, thalamic and amygdala connections. 

These models are used to investigate the anatomical substrates for potential interactions between reward, cognition and motor control areas that underlie the development of goal-directed behaviors and habit formation. 

Moreover, the development of rodent, primate and human models allow species comparison of these complex networks.  In collaboration with several clinical groups, this work is used to inform new therapeutic approaches, such as deep brain stimulation, and in the interpretation of human imaging studies. 

Our studies use conventional tracing methods to examine the organization of pathways within the cortico-basal ganglia-thalamic/midbrain network; and immunohistochemical studies to examine pathways, transmitter and receptor distributions, and specific cell populations within the network. The results from individual experiments are then merged with other experiments to produce an interactive model system in which different parameters and relationships between parameters can be examined in more detail.

Haber SN, Fudge JL, and McFarland NR  (2000)  Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum.  J. Neurosci. 20:2369-2382.

Fudge JL, Kunishio K, Walsh P, Richard C, and Haber SN  (2002)  Amygdaloid projections to ventromedial striatial subterritories in the primate.  Neuroscience 110:257-275.

McFarland NR, and Haber SN  (2002)  Thalamic relay nuclei of the basal ganglia form both reciprocal and nonreciprocal cortical connections, linking multiple frontal cortical areas.  J. Neurosci. 22:8117-8132.

Haber SN  (2003)  The primate basal ganglia: parallel and integrative networks.  J. Chem. Neuroanat. 26:317-330.

Hurley SD, O’Banion MK, Song DD, Arana FS, Olschowka JA, and Haber SN  (2003)  Microglial response is poorly correlated with neurodegeneration following chronic, low-dose MPTP administration in monkeys.  Exp. Neurol. 184:659-668.

Frankle WG, Laruelle M, and Haber SN  (2006)  Prefrontal cortical projections to the midbrain in primates: evidence for a sparse connection.  Neuropsychopharmacology 31:1627-1636.

Shapira NA, Okun MS, Wint D, Foote KD, Byars JA, Bowers D, Springer US, Lang PJ, Greenberg BD, Haber SN, and Goodman WK  (2006)  Panic and fear induced by deep brain stimulation.  J. Neurol. Neurosurg. Psychiatry 77:410-412.

Rauch SL, Dougherty DD, Malone D, Rezai A, Friehs G, Fischman AJ, Alpert NM, Haber SN, Stypulkowski PH, Rise MT, Rasmussen SA, and Greenberg BD  (2006)  A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder.  J. Neurosurg. 104:558-565.

Heimer G, Rivlin-Etzion M, Bar-Gad I, Goldberg JA, Haber SN, and Bergman H.  (2006)  Dopamine replacement therapy does not restore the full spectrum of normal pallidal activity in the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine primate model of Parkinsonism.  J. Neurosci. 26:8101-8114.

Haber SN, Kim KS, Mailly P, and Calzavara R  (2006)  Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning.  J. Neurosci. 26:8368-8376.