Yale University, New Haven CT
Government Grants Promoting Cruelty to Animals
Yale University, New Haven CT
David A. McCormick - Feline Testing - 1999
Abstract: DESCRIPTION (provided by applicant): The receptive field properties of visual cortical neurons are dynamic and can be altered both in space and time, in response to the pattern of activation to which the cell is exposed. Dynamical changes in receptive field properties are likely to contribute to several perceptual phenomena such as fill-in, afterimages, and contour integration. Until recently, the cellular mechanisms of these dynamic changes in cortical function have been difficult to examine. However, the application of intracellular recording techniques promises to determine at least some of the mechanisms underlying visual cortical plasticity.
For example, through intracellular recordings we have shown that stimulation of cortical neurons with a high contrast stimulus results in the hyperpolarization of the membrane potential, apparently through the activation of intrinsic K+ conductances. This hyperpolarization is, at least in part, responsible for the shift in contrast response function that underlies contrast adaptation. Conversely, withdrawal of the high contrast stimulus results in a gradual depolarization of the cell, with opposite effects.
In our preliminary experiments, we have observed that these changes in membrane potential not only change the amplitude of the visually evoked response, but also the shape of the receptive field. Membrane potential depolarization of cortical neurons results in an expansion of the receptive field size as well as an increase in the amplitude of visually evoked responses. Through this mechanism, presentation of an artificial scotoma (after stimulation of the receptive field) results in a gradual depolarization of the membrane potential and an expansion of the receptive field over a period of about 2-20 seconds.
This time frame is remarkably similar to that associated with perceptual fill-in during the presentation of artificial scotomas in humans. Results from previous extracellular recording studies in vivo suggest that these perceptual phenomenon are mediated in large part through local and medium range (mm) horizontal interactions in the visual cortex. We suggest that regulation of membrane potential in cortical neurons may not only critically determine the response properties of the neuron under investigation, but also determine the interactions of cells in the local neocortical circuit, and contribute strongly to time and space-dependent dynamics of receptive field properties. Here we will test this hypothesis using intracellular recording studies in vivo in conjunction with visual stimulation.
The ionic mechanisms of these effects will also be examined in detail with in vitro recording techniques. Through these studies, we will begin to achieve a cellular level understanding of visual perceptual mechanisms and fast (seconds) cortical plasticity.
Role of Synaptic and Intrinsic Membrane Properties in Short-Term Receptive Field Dynamics in Cat Area 17
Lionel G. Nowak, Maria V. Sanchez-Vives, and David A. McCormick
Department of Neurobiology and the Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510
The Journal of Neuroscience, February 16, 2005, 25(7):1866-1880; doi:10.1523/JNEUROSCI.3897-04.2005
Animal preparation. The protocols for animal preparation, electrophysiological recordings, and data acquisition have been detailed previously (Sanchez-Vives et al., 2000a). Anesthesia was induced in adult cats (2.5-3.5 kg) with ketamine (12-15 mg/kg, i.m.) and xylazine (1 mg/kg, i.m.). Atropine (0.05 mg/kg, s.c.) was given to reduce secretions. A forelimb vein was cannulated for intravenous perfusion, a tracheal tube was inserted for active ventilation, and wires were placed through the skin for electrocardiogram (ECG) recording.
The cat was mounted in a stereotaxic frame and ventilated with a mixture of nitrous oxide and oxygen (2:1) with halothane (1.5% during surgery). Two wires were inserted over the frontal cortex for epidural EEG recording.
To minimize movements resulting from respiration and heart pulsation, a cisternal drainage and a bilateral pneumothorax were performed, and the animal was suspended by the rib cage to the stereotaxic frame.
A craniotomy (3-4 mm wide) was made over the area centralis representation of area 17. After surgery, the animals were paralyzed with either Pavulon (0.3 mg/kg for induction, followed by a continuous perfusion of 0.3 mg · kg-1 · h-1) or Norcuron (0.15 mg/kg for induction, followed by a continuous perfusion of 0.1 mg · kg-1 · h-1).
The nictitating membranes were retracted using ophthalmic phenylephrine, and the pupils were dilated and accommodation paralyzed with ophthalmic atropine. Area centralis and the optic discs were localized by back projection. The eyes were focused onto a computer monitor at 114 cm using corrective, gas-permeable contact lenses. No artificial pupils were used.
During recording, anesthesia was maintained with 0.4-1% halothane in nitrous oxide/oxygen (2:1). The heart rate, expiratory CO2 concentration, rectal temperature, and blood O2 concentration were monitored throughout the experiment and maintained at 150-180 beats per minute, 3-4%, 37-38°C, and >95% respectively. The state of the animal was monitored regularly through the EEG and ECG and the absence of reaction to noxious stimuli. This protocol was approved by the Yale University Institutional Animal Care and Use Committees and conforms to the guidelines recommended in Preparation and Maintenance of Higher Mammals during Neuroscience Experiments (National Institutes of Health publication 91-3207).
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