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main page
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lab members
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research projects
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publications
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videos
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links
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Some of our research projects
I - Electrophysiology of the Prefrontal Cortex (MH57683)
In vivo dopaminergic effects in the prefrontal cortex. The actions of dopaminergic
inputs to prefrontal pyramidal neurons are being studied with in vivo intracellular
and juxtacellular recordings. Left: Example of a neuron recorded from the medial
PFC and filled with Neurobiotin; superimposed, a tracing showing the spontaneous
alternations
in
the membrane potential between UP and DOWN states. Afferents from the ventral
tegmental area modulate membrane potential state transitions and cell firing
in the PFC (B.L.Lewis) and juxtacellular recordings
revealed an activation of fast-spiking interneurons (K.Toreson;
KYTseng). Local inhibition seems to have a critical role in the actions of
dopamine in this important brain region. Supported by MH57683.
Cerebral Cortex 10 (2000) 1168-1175
Electrophysiological
PFC alterations in animals with a neonatal ventral hippocampal lesion. A
neonatal hippocampal lesion has been proposed as an animal model of schizophrenia.
This
model has shown behavioral deficits in adult, but not prepubertal animals, indicating
that changes may remain latent. We are studying a number of electrophysiological
parameters in such animals and their controls. The figure shows an example of
hippocampal lesion in an animal from which a PFC neuron with UP and DOWN states
in its membrane potential was also observed. The changes in PFC pyramidal neurons
to activation of their dopamine afferents are under study (B.L.
Lewis). Similar experiments were conducted in the nucleus accumbens
of these animals and their controls. An alteration in the response of accumbens
neurons
to VTA stimulation was observed, probably secondary to a prefrontal deficit (Y.
Goto). This research was expanded with in vitro recordings from prefrontal
cortical neurons from lesioned animals and controls, assessing changes in dopamine-glutamate
interactions (KY Tseng). Supported by MH57683. Cerebral
Cortex 12 (2002) 975-982
Journal
of Neuroscience 22 (2002) 9070-9077
Biological Psychiatry 55 (2004) 172-176
Prefrontal
cortical-VTA synchrony. The interactions between the PFC and dopaminergic
neurons in the VTA are being studied with simultaneous dual recordings
from
both regions in vivo. Emphasis is being placed on synchrony of oscillations
in both areas. The pathways and receptor subtypes involved in this synchrony
are being determined (Y. Peters). This is being also continued
with multichannel recordings in freely moving animals, as a collaboration with
Dr. Regina Carelli from the University of North Carolina. Supported by MH57683.
Dopamine-glutamate-GABA
interactions in the prefrontal cortex and adolescence. The interactions
between monoamines and glutamate receptors in the control of cell excitability
of
PFC neurons
is being studied in vitro with IR-DIC whole-cell clamp recording
techniques. (J Wang; KY Tseng). The modulation of
interneurons is also pursued. A particularly interesting finding is that
the DA effects on interneurons change dramatically during adolescence (KY
Tseng). Supported by MH57683 and a NARSAD Independent Investigator Award.
Cerebral
Cortex 11 (2001) 452-462
Journal of Neuroscience 24 (2004) 5131-5139
Cerebral Cortex 15 (2005) 49-57
Cerebral Cortex (2007) Advance Access published on July 3, 2006; doi: doi:10.1093/cercor/bhl034
Dopaminergic control of responses to amygdala stimulation in the prefrontal cortex. In vivo intracellular recordings are used to test the modulation of amygdala-PFC responses by endogenous dopamine by VTA stimulation (J. Dilgen). Supported by MH57683.
Persistent activity in PFC neurons in vitro. Plateau depolarization
resembling in vivo up states are being studied in slices with co-activation
of D1 and NMDA receptors. This phenomenon is only observed in slices from mature animals
(KY Tseng). Similar experiments are being conducted
in organotypic cortex-striatum-nigra co-cultures, assessing the role of the
dopaminergic innervation on striatal
persistent activity (KY Tseng; in collaboration with
Abigail Snyder-Keller). Supported by MH57683 and a NARSAD Independent Investigator
Award.
Cerebral Cortex 15 (2005) 49-57
Metabolic changes in animals with a neonatal hippocampal lesion. Metabolic
markers are being used to determine changes in activity in this animal model
(F. Amin; KY Tseng; BL
Lewis). Supported by MH57683.
Biological Psychiatry 60 (2006) 585-590
II - Information Processing in the Nucleus Accumbens (MH60131)
Hippocampal
and prefrontal gating of accumbens neural ensembles.
The network properties of neural ensembles in the hippocampal-accumbens system
were studied with simultaneous
recordings
from these regions. The integration of this information within the accumbens
with that arising from the amygdala, thalamus and prefrontal cortex was
addressed using a variety of statistical and mathematical tools (Y.
Goto). The role of bursting PFC activity on accumbens information processing
is being studied with in vitro, in vivo anesthetized experiments and multichannel
recordings from awake, freely moving animals (A. Gruber; R Hussain). Supported
by MH60131.
Journal
of Neuroscience 21 (2001) 4498-4504.
Journal
of Neuroscience 20 (2001) RC131.
PNAS
99 (2002) 13189-13193.
Dopamine-glutamate interactions in the nucleus accumbens. Whole-cell recordings are being used to address the dopaminergic modulation of glutamatergic responses in the nucleus accumbens. Emphasis is placed on endogenous release of dopamine. (M.Benoit-Marand). A collaboration with John Wolf/Leif Finkel (UPenn) focused on assessing the role of NMDA/non-NMDA activity on accumbens neurons up states using computer models based on real data (M Benoit-Marand). Supported by MH60131
Journal of Neuroscience 25 (2005) 9080-9095.
Persistent activity in corticostriatal and cortico-cortical responses. Whole cell recordings of medium spiny neurons in the caudate-putamen are being employed to test the role of cortical inputs in driving persistent depolarizations. (F. Kasanetz; in collaboration with Dr. Gustavo Murer, Dept. Fisiologia, Univ. Buenos Aires, Argentina). Supported by MH60131.
Journal of Physiology 577 (2006) 97-113.
III - Electrophysiology of Behavioral Sensitization (DA14020)
Behavioral
sensitization and responses to VTA stimulation. The interactions among
the prefrontal cortex, nucleus accumbens and dopamine cells involved in development
and
expression
of behavioral sensitization to repeated methamphetamine administration are
being studied with electrical stimulation of dopamine cells in
sensitized
and non-sensitized animals. Behavioral sensitization is the increased locomotor
response to psychostimulants that is typically observed following repeated
intermittent
administration. This phenomenon is supposed to be related to drug craving in
addiction. (A.M. Brady). In addition, the role of
the dopaminergic innervation of the accumbens on the response of these
neurons to excitatory afferents is being studied
with
in vivo intracellular recordings (AM Brady) Supported
by DA14020.
Journal
of Neuroscience 24 (2004) 1040-1049.
Synchrony among prefrontal cortex, accumbens and ventral tegmental area in behavioral sensitization. Simultaneous recordings in all three areas affected in this phenomenon are being conducted to determine long-term changes (N. Barnhardt). Supported by DA14020.