Peter Shizgal | Concordia University (Canada) (original) (raw)

Papers by Peter Shizgal

The Journal of Neuroscience the Official Journal of the Society For Neuroscience, Apr 1, 1986

Frontiers in Behavioral Neuroscience, 2014

Frontiers in behavioral neuroscience, 2015

Adult rats emit ultrasonic vocalizations (USVs) at around 50-kHz; these commonly occur in context... more Adult rats emit ultrasonic vocalizations (USVs) at around 50-kHz; these commonly occur in contexts that putatively engender positive affect. While several reports indicate that dopaminergic (DAergic) transmission plays a role in the emission of 50-kHz calls, the pharmacological evidence is mixed. Different modes of dopamine (DA) release (i.e., tonic and phasic) could potentially explain this discrepancy. To investigate the potential role of phasic DA release in 50-kHz call emission. In Experiment 1, USVs were recorded in adult male rats following unexpected electrical stimulation of the medial forebrain bundle (MFB). In parallel, phasic DA release in the nucleus accumbens (NAcc) was recorded using fast-scan cyclic voltammetry. In Experiment 2, USVs were recorded following response-contingent or non-contingent optogenetic stimulation of midbrain DAergic neurons. Four 20-s schedules of optogenetic stimulation were used: fixed-interval, fixed-time, variable-interval, and variable-time....

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

$Research paper thumbnail of Effects of NMDA Lesions of the Medial Basal Forebrain on LH and VTA Self-Stimulation - Comparison of psychophysical and electrophysiological estimates of refractory periods$

Physiology & Behavior

ARVANITOGIANNIS, A., L. RISCALDINO AND P. SHIZGAL. Effects of NMDA lesions of the medial basal fo... more ARVANITOGIANNIS, A., L. RISCALDINO AND P. SHIZGAL. Effects of NMDA lesions of the medial basal forebrain on LH and VTA self-stimulation. PHYSIOL BEHAV 65 (4/5) 805-810, 1999.-Rewarding stimulation of the medial forebrain bundle (MFB) increases Fos-like immunoreactivity in many brain areas, including an ipsilateral, basal forebrain region extending from the medial preoptic area (MPO) to the lateral preoptic area, and substantia innominata. Excitotoxic lesions of the lateral portion of this region have been found to produce large sustained or transient increases in the number of pulses required to maintain half-maximal lever-pressing (required number of pulses) for MFB stimulation. In the present study, changes in self-stimulation of the lateral hypothalamus and ventral tegmental area were assessed following excitotoxic lesions of more medial structures, including the MPO and bed nucleus of the stria terminalis. Increases in the required number of pulses (up to 0.16 log 10 units) were seen in only 2 of 10 subjects. In two other rats, the reward effectiveness of the stimulation was moderately increased after the lesion as manifested in decreases of up to 0.14 log 10 units in the required number. No appreciable change from baseline was seen in the remaining six subjects. The simplest interpretation of these results is that neurons with cell bodies in the medial portion of the basal forebrain may make a smaller contribution to the rewarding effect of MFB stimulation than neurons in the lateral portion. © 1999 Elsevier Science Inc.

Behavioural brain research, Jan 22, 2015

Mesocortical dopamine connectivity continues to mature during adolescence. This protracted develo... more Mesocortical dopamine connectivity continues to mature during adolescence. This protracted development confers increased vulnerability for environmental and genetic factors to disrupt mesocortical wiring and subsequently influence responses to drugs of abuse in adulthood. The netrin-1 receptor, DCC, orchestrates medial prefrontal cortex dopamine input during adolescence and dictates the functional organization of local circuitry. Haploinsufficiency of dcc results in increased dopamine innervation to the medial prefrontal cortex, which in turn leads to resilience against the behavioral activating effects of stimulant drugs. However, whether sensitivity to the rewarding effects of drugs of abuse is also altered in dcc haploinsufficiency remains to be resolved. Here, we used the curve-shift method to measure cocaine-induced facilitation of intracranial self-stimulation (ICSS) in adult dcc haploinsufficient mice and wild-type littermates. We found that dcc haploinsufficient mice acquire...

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

Dopaminergic neurons contribute to intracranial self-stimulation (ICSS) and other reward-seeking ... more Dopaminergic neurons contribute to intracranial self-stimulation (ICSS) and other reward-seeking behaviors, but it is not yet known where dopaminergic neurons intervene in the neural circuitry underlying reward pursuit or which psychological processes are involved. In rats working for electrical stimulation of the medial forebrain bundle, we assessed the effect of GBR-12909 (1-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-4-[3-phenylpropyl]piperazine), a specific blocker of the dopamine transporter. Operant performance was measured as a func-tion of the strength and cost of electrical stimulation. GBR-12909 increased the opportunity cost most subjects were willing to pay for a reward of a given intensity. However, this effect was smaller than that produced by a regimen of cocaine administration that drove similar increases in nucleus accumbens (NAc) dopamine levels in unstimulated rats. Delivery of rewarding stimulation to drug-treated rats caused an additional increase in dopamine concent...

Behavioural Brain Research, 2015

ABSTRACT The rewarding effect of electrical brain stimulation has been studied extensively for 60... more ABSTRACT The rewarding effect of electrical brain stimulation has been studied extensively for 60 years, yet the identity of the underlying neural circuitry remains unknown. Previous experiments have characterized the directly stimulated ("first-stage") neurons implicated in self-stimulation of the medial forebrain bundle. Their properties are consistent with those of fine myelinated axons, at least some of which project rostro-caudally. These properties do not match those of dopaminergic neurons. The present psychophysical experiment estimates an additional first-stage characteristic: maximum firing frequency. We test a frequency-following model that maps the experimenter-set pulse frequency into the frequency of firing induced in the directly stimulated neurons. As pulse frequency is increased, firing frequency initially increases at the same rate, then becomes probabilistic, and finally levels off. The frequency-following function is based on the counter model which holds that the rewarding effect of a pulse train is determined by the aggregate spike rate triggered in first-stage neurons during a given interval. In 7 self-stimulating rats, we measured current-versus-pulse-frequency trade-off functions. The trade-off data were well described by the frequency-following model, and its upper asymptote was approached at a median value of 362Hz (IQR=46Hz). This value implies a highly excitable, non-dopaminergic population of first-stage neurons. Incorporating the frequency-following function and parameters in Shizgal's 3-dimensional reward-mountain model improves its accuracy and predictive power. Copyright © 2015. Published by Elsevier B.V.

Encyclopedia of Psychopharmacology, 2010

MethodsX, 2015

In vivo optogenetic experiments commonly employ long lengths of optical fiber to connect the ligh... more In vivo optogenetic experiments commonly employ long lengths of optical fiber to connect the light source (commonly a laser) to the optical fiber implants in the brain. Commercially available patch cords are expensive and break easily. Researchers have developed methods to build these cables in house for in vivo experiments with rodents [1-4]. However, the half-life of those patch cords is greatly reduced when they are used with behaving rats, which are strong enough to break the delicate cable tip and to bite through the optical fiber and furcation tubing. Based on [3] we have strengthened the patch-cord tip that connects to the optical implant, and we have incorporated multiple layers of shielding to produce more robust and resistant cladding. Here, we illustrate how to build these patch cords with FC or M3 connectors. However, the design can be adapted for use with other common optical-fiber connectors. We have saved time and money by using this design in our optical selfstimulation experiments with rats, which are commonly several months long and last four to eleven hours per session. The main advantages are:

Behavioral biology, 1978

ABSTRACT

PLoS computational biology, 2014

Given the option, humans and other animals elect to distribute their time between work and leisur... more Given the option, humans and other animals elect to distribute their time between work and leisure, rather than choosing all of one and none of the other. Traditional accounts of partial allocation have characterised behavior on a macroscopic timescale, reporting and studying the mean times spent in work or leisure. However, averaging over the more microscopic processes that govern choices is known to pose tricky theoretical problems, and also eschews any possibility of direct contact with the neural computations involved. We develop a microscopic framework, formalized as a semi-Markov decision process with possibly stochastic choices, in which subjects approximately maximise their expected returns by making momentary commitments to one or other activity. We show macroscopic utilities that arise from microscopic ones, and demonstrate how facets such as imperfect substitutability can arise in a more straightforward microscopic manner.

Journal of comparative and physiological psychology, 1980

Rats lever pressed for concurrent electrical stimulation of the lateral hypothalamus and ventral ... more Rats lever pressed for concurrent electrical stimulation of the lateral hypothalamus and ventral tegmentum. The pulse-pair stimulation technique was used, with the first pulse of each pair applied to one electrode and the second to the other electrode; the intrapair interval was varied. The effectiveness of stimulation, measured behaviorally, increased abruptly (within .4 msec) as the intrapair interval was increased in the range from 1.0 to 2.0 msec. These results, which do not resemble single-electrode refractory period results, are interpreted as evidence of collision in the directly stimulated, reward-related neurons linking the two sites. We conclude that self-stimulation of the medial forebrain bundle involves the direct activation of long-axon, longitudinal pathways. Estimates of the conduction velocity in the fibers subserving the collision-like effects are consistent with the properties of small myelinated axons but not central monoaminergic fibers.

The Journal of neuroscience : the official journal of the Society for Neuroscience, 1986

The role of ascending and descending fibers in self-stimulation of the lateral hypothalamus and v... more The role of ascending and descending fibers in self-stimulation of the lateral hypothalamus and ventral tegmental area in the rat was assessed by noting whether anodal hyperpolarization of one of these sites could reduce the rewarding effect of stimulating the other site. Strength-duration curves were obtained by psychophysical means, with one of the depth electrodes serving as the cathode and the other as the anode. It was anticipated that at long pulse durations, conduction in some of the fibers stimulated at the cathode would be blocked at the anode. At shorter durations, the anodal hyperpolarization should have dissipated before the arrival of the action potentials triggered by the cathode. Thus, the predicted effect of the block was to bend the strength-duration curves obtained with two depth electrodes upward at long pulse durations, provided that the anode lay between the cathode and the efferent stages of the pathway responsible for the rewarding effect. To control for possi...

The Journal of Neuroscience the Official Journal of the Society For Neuroscience, Apr 1, 1986

Frontiers in Behavioral Neuroscience, 2014

Frontiers in behavioral neuroscience, 2015

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

Physiology & Behavior

Behavioural brain research, Jan 22, 2015

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

Behavioural Brain Research, 2015

Encyclopedia of Psychopharmacology, 2010

MethodsX, 2015

Behavioral biology, 1978

ABSTRACT

PLoS computational biology, 2014

Journal of comparative and physiological psychology, 1980

The Journal of neuroscience : the official journal of the Society for Neuroscience, 1986

Dividing limited time between work and leisure when both have their attractions is a common every... more Dividing limited time between work and leisure when both have their attractions is a common everyday decision. We provide a normative control-theoretic treatment of this decision that bridges economic and psychological accounts. We show how our framework applies to free-operant behavioural experiments in which subjects are required to work (depressing a lever) for sufficient total time (called the price) to receive a reward. When the microscopic benefit-of-leisure increases nonlinearly with duration, the model generates behaviour that qualitatively matches various microfeatures of subjects’ choices, including the distribution of leisure bout durations as a function of the pay-off. We relate our model to traditional accounts by deriving macroscopic, molar, quantities from microscopic choices.

PloS one, Jan 1, 2010

Dopamine-containing neurons have been implicated in reward and decision making. One element of th... more Dopamine-containing neurons have been implicated in reward and decision making. One element of the supporting evidence is that cocaine, like other drugs that increase dopaminergic neurotransmission, powerfully potentiates reward seeking. We analyze this phenomenon from a novel perspective, introducing a new conceptual framework and new methodology for determining the stage(s) of neural processing at which drugs, lesions and physiological manipulations act to influence reward-seeking behavior. Cocaine strongly boosts the proclivity of rats to work for rewarding electrical brain stimulation. We show that the conventional conceptual framework and methods do not distinguish between three conflicting accounts of how the drug produces this effect: increased sensitivity of brain reward circuitry, increased gain, or decreased subjective reward costs. Sensitivity determines the stimulation strength required to produce a reward of a given intensity (a measure analogous to the K M of an enzyme) whereas gain determines the maximum intensity attainable (a measure analogous to the v max of an enzyme-catalyzed reaction). To distinguish sensitivity changes from the other determinants, we measured and modeled reward seeking as a function of both stimulation strength and opportunity cost. The principal effect of cocaine was a two-fourfold increase in willingness to pay for the electrical reward, an effect consistent with increased gain or decreased subjective cost. This finding challenges the long-standing view that cocaine increases the sensitivity of brain reward circuitry. We discuss the implications of the results and the analytic approach for theories of how dopaminergic neurons and other diffuse modulatory brain systems contribute to reward pursuit, and we explore the implications of the conceptual framework for the study of natural rewards, drug reward, and mood.