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1.
Neuroscience ; 247: 395-411, 2013 Sep 05.
Article in English | MEDLINE | ID: mdl-23660194

ABSTRACT

Recent in vivo data show ensemble activity in medial entorhinal neurons that demonstrates 'look-ahead' activity, decoding spatially to reward locations ahead of a rat deliberating at a choice point while performing a cued, appetitive T-Maze task. To model this experiment's look-ahead results, we adapted previous work that produced a model where scans along equally probable directions activated place cells, associated reward cells, grid cells, and persistent spiking cells along those trajectories. Such look-ahead activity may be a function of animals performing scans to reduce ambiguity while making decisions. In our updated model, look-ahead scans at the choice point can activate goal-associated reward and place cells, which indicate the direction the virtual rat should turn at the choice point. Hebbian associations between stimulus and reward cell layers are learned during training trials, and the reward and place layers are then used during testing to retrieve goal-associated cells based on cue presentation. This system creates representations of location and associated reward information based on only two inputs of heading and speed information which activate grid cell and place cell layers. We present spatial and temporal decoding of grid cell ensembles as rats are tested with perfect and imperfect stimuli. Here, the virtual rat reliably learns goal locations through training sessions and performs both biased and unbiased look-ahead scans at the choice point. Spatial and temporal decoding of simulated medial entorhinal activity indicates that ensembles are representing forward reward locations when the animal deliberates at the choice point, emulating in vivo results.


Subject(s)
Entorhinal Cortex/physiology , Learning , Models, Neurological , Neural Networks, Computer , Maze Learning/physiology
2.
Neuroscience ; 149(4): 760-7, 2007 Nov 23.
Article in English | MEDLINE | ID: mdl-17964734

ABSTRACT

Acetylcholine may help set the dynamics within neural systems to facilitate the learning of new information. Neural models have shown that if new information is encoded at the same time as retrieval of existing information that is already stored, the memories will interfere with each other. Structures such as the hippocampus have a distinct laminar organization of inputs that allows this hypothesis to be tested. In region CA1 of the rat (Sprague Dawley) hippocampus, the cholinergic agonist carbachol (CCh) suppresses transmission in stratum radiatum (SR), at synapses of the Schaffer collateral projection from CA3, while having lesser effects in stratum lacunosum-moleculare (SLM), the perforant path projection from entorhinal cortex (Hasselmo and Schnell, 1994). The current research extends support of this selectivity by demonstrating laminar effects in region CA3. CCh caused significantly greater suppression in SR than in SLM at low concentrations, while the difference in suppression was not significant at higher concentrations. Differences in paired-pulse facilitation suggest presynaptic inhibition substantially contributes to the suppression and is highly concentration and stratum dependent. This selective suppression of the recurrent excitation would be appropriate to set CA3 dynamics to prevent runaway modification of the synapses of excitatory recurrent collaterals by reducing the influence of previously stored associations and allowing incoming information from the perforant path to have a predominant influence on neural activity.


Subject(s)
Acetylcholine/pharmacology , Glutamic Acid/pharmacology , Hippocampus/cytology , Neural Inhibition/drug effects , Synapses/drug effects , Synaptic Transmission/drug effects , Animals , Corpus Striatum/physiology , Corpus Striatum/radiation effects , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Electric Stimulation/methods , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/radiation effects , Hippocampus/drug effects , In Vitro Techniques , Male , Neural Inhibition/physiology , Perforant Pathway/drug effects , Perforant Pathway/physiology , Perforant Pathway/radiation effects , Rats , Rats, Sprague-Dawley , Synapses/radiation effects , Synaptic Transmission/radiation effects
3.
J Mol Neurosci ; 30(1-2): 133-5, 2006.
Article in English | MEDLINE | ID: mdl-17192659

ABSTRACT

Extensive physiological research has demonstrated a number of common effects of acetylcholine within cortical structures, including the hippocampus, piriform cortex, and neocortex (Hasselmo, 1995, 1999). This article will provide a description of how the different physiological effects of acetylcholine could interact to alter specific functional properties of the cortex. The physiological effects of acetylcholine serve to enhance the influence of feed- forward afferent input to the cortex while decreasing background activity by suppressing excitatory feedback connections within cortical circuits. By enhancing the response to sensory input, high levels of acetylcholine enhance attention to sensory stimuli in the environment and enhance encoding of memory for specific stimuli. Interference from prior memory is reduced by suppressing synapses modified by prior learning (Sevilla et al., 2002; Linster et al., 2003).


Subject(s)
Cerebral Cortex/physiology , Cholinergic Agents/pharmacology , Acetylcholine/pharmacology , Acetylcholine/physiology , Animals , Cerebral Cortex/drug effects , Feedback , Models, Neurological , Synapses/drug effects , Synapses/physiology
4.
Neurobiol Learn Mem ; 85(2): 153-63, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16290192

ABSTRACT

Cholinergic modulation of synaptic transmission is vital to memory processes and may be responsible for setting network dynamics in the hippocampus appropriate for encoding of information. found evidence suggesting M1 receptors cause presynaptic inhibition of glutamatergic transmission, while research supports a role of the M2 receptor. We examined muscarinic inhibition of fEPSPs in stratum radiatum of mice lacking m1 subtype receptors (KO) compared to wild type (WT) controls. WT mice exhibit greater suppression of transmission by muscarine as compared to KO in a dose dependent fashion. Oxotremorine shows no significant difference in suppression between WT and KO, while MCN-A-343, an M1 agonist, exhibits a significant difference between KO and WT, with KO showing no suppression. One hundred micromolar SGS-742, a selective GABA(B) antagonist, fails to affect either normal transmission or muscarinic suppression in either WT or KO suggesting that differences in suppression between the groups is not attributable to differences in GABA(B) receptor activation due to muscarinic activation of GABAergic interneurons. These findings support a role for presynaptic m1 mAChRs in modulation of synaptic transmission in CA1, but indicate that other muscarinic receptor subtypes, such as M2, are also involved in suppression of synaptic potentials.


Subject(s)
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride/pharmacology , GABA Antagonists/pharmacology , Hippocampus/drug effects , Muscarinic Agonists/pharmacology , Organophosphorus Compounds/pharmacology , Receptor, Muscarinic M1/drug effects , Receptors, GABA-B/drug effects , Receptors, Presynaptic/drug effects , Synaptic Transmission/drug effects , Animals , Dose-Response Relationship, Drug , Evoked Potentials/drug effects , In Vitro Techniques , Interneurons/drug effects , Mice , Mice, Knockout , Nerve Net/drug effects , Receptor, Muscarinic M1/genetics
5.
J Neurophysiol ; 86(4): 1792-802, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11600640

ABSTRACT

Activation of muscarinic receptors and GABA(B) receptors causes presynaptic inhibition of glutamatergic synaptic potentials at excitatory feedback connections in cortical structures. These effects may regulate dynamics in cortical structures, with presynaptic inhibition allowing extrinsic afferent input to dominate during encoding, while the absence of presynaptic inhibition allows stronger excitatory feedback during retrieval or consolidation. However, proposals for a functional role of such modulatory effects strongly depend on the time course of these modulatory effects; how rapidly can they turn off and on? In brain slice preparations of hippocampal region CA1, we have explored the time course of suppression of extracellularly recorded synaptic potentials after pressure pulse application of acetylcholine and GABA. Acetylcholine causes suppression of extracellular potentials with onset time constants between 1 and 2 s, and decay constants ranging between 10 and 20 s, even with very brief injection pulses. GABA causes suppression of extracellular potentials with onset time constants between 0.2 and 0.7 s, and decay time constants that decrease to values shorter than 2 s for very brief injection pulses. These techniques do not give an exact measure of the physiological time course in vivo, but they give a notion of the relative time course of the two modulators. The slow changes due to activation of muscarinic acetylcholine receptors may alter the dynamics of cortical circuits over longer intervals (e.g., between different stages of waking and sleep), setting dynamics appropriate for encoding versus consolidation processes. The faster changes in synaptic potentials caused by GABA could cause changes within each cycle of the theta rhythm, rapidly switching between encoding and retrieval dynamics during exploration.


Subject(s)
Acetylcholine/pharmacology , Dentate Gyrus/physiology , gamma-Aminobutyric Acid/pharmacology , Animals , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Female , Organ Culture Techniques , Rats , Rats, Sprague-Dawley , Reaction Time/physiology , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Time Factors
6.
Hippocampus ; 11(4): 337-46, 2001.
Article in English | MEDLINE | ID: mdl-11530838

ABSTRACT

Lesions of parahippocampal structures impair performance of delayed matching tasks in nonhuman primates, suggesting a role for these structures in the maintenance of items in working memory and short-term stimulus matching. However, most human functional imaging studies have not shown medial temporal activation during working memory tasks and have primarily focused on functional magnetic resonance imaging (fMRI) signal intensity changes in the prefrontal and posterior parietal cortex. The goal of this study was to test the hypothesis that the difference between the human and nonhuman primate data results from the use of highly familiar stimuli in human working memory studies and trial-unique stimuli in nonhuman primate studies. We used fMRI to examine prefrontal and temporal lobe activation during performance of a working memory (two-back) task, using blocks of novel and highly familiar complex pictures. Performance of the working memory task with novel complex pictures resulted in greater signal change within medial temporal lobe structures than performance of the task with familiar complex pictures. In contrast, the working memory task with highly familiar stimuli resulted in greater prefrontal activation. These results are consistent without hypothesis that the medial temporal lobe is recruited for the short-term maintenance of information that has no prior representation in the brain, whereas the prefrontal cortex is important for monitoring familiar stimuli that have a high degree of interference. A second set of tasks examined stimulus matching. Subjects performed a target-matching task, during which they identified a single target presented in blocks of novel or familiar stimuli. The results provide evidence of hippocampal and parahippocampal recruitment in the target-matching task with familiar stimuli. These results are consistent with prior animal studies and suggest that prefrontal regions may be important for the monitoring and matching of familiar stimuli which have a high potential for interference, whereas medial temporal regions may become proportionally more important for matching and maintenance of novel stimuli.


Subject(s)
Memory/physiology , Prefrontal Cortex/physiology , Temporal Lobe/physiology , Adult , Behavior/physiology , Brain Mapping , Female , Humans , Magnetic Resonance Imaging , Male , Mental Recall/physiology , Photic Stimulation
7.
Behav Neurosci ; 115(4): 826-33, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11508721

ABSTRACT

The neuromodulator acetylcholine is thought to modulate information processing in the olfactory system. The authors used 192 IgG-saporin, a lesioning agent selective for basal forebrain cholinergic neurons, to determine whether selective lesions of cholinergic neurons projecting to the olfactory bulb and cortex affect odor perception in rats. Lesioned and sham-operated rats were tested in an olfactory generalization paradigm with sets of chemically related odorants (n-aliphatic aldehydes, acids, and alcohols). Lesioned rats generalized more between chemically similar odorants but did not differ from controls in their response to chemically unrelated odorants or in acquisition of the conditioned odor. Results show that cholinergic inputs to the olfactory system influence perceptual qualities of odorants and confirm predictions made by computational models of this system.


Subject(s)
Acetylcholine/physiology , Odorants , Olfactory Bulb/physiology , Olfactory Receptor Neurons/physiology , Smell/physiology , Animals , Brain Chemistry , Choice Behavior/physiology , Cholinergic Antagonists/pharmacology , Generalization, Stimulus/physiology , Male , Olfactory Receptor Neurons/pathology , Prosencephalon/physiology , Rats , Rats, Sprague-Dawley
8.
Chem Senses ; 26(5): 585-94, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11418504

ABSTRACT

Acetylcholine and norepinephrine have a number of effects at the cellular level in the piriform cortex. Acetylcholine causes a depolarization of the membrane potential of pyramidal cells and interneurons, and suppresses the action potential frequency accommodation of pyramidal cells. Acetylcholine also has strong effects on synaptic transmission, suppressing both excitatory and inhibitory synaptic transmission. At the same time as it suppresses synaptic transmission, acetylcholine enhances synaptic modification, as demonstrated by experiments showing enhancement of long-term potentiation. Norepinephrine has similar effects. In this review, we discuss some of these different cellular effects and provide functional proposals for these individual effects in the context of the putative associative memory function of this structure.


Subject(s)
Norepinephrine/physiology , Olfactory Pathways/physiology , Synaptic Transmission/physiology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Cholinergic Agents/pharmacology , Discrimination Learning/physiology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Neurotransmitter Agents/pharmacology , Neurotransmitter Agents/physiology , Norepinephrine/pharmacology , Rats , Synaptic Transmission/drug effects
9.
Behav Neurosci ; 115(2): 314-27, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11345957

ABSTRACT

E. De Rosa and M. E. Hasselmo (2000) demonstrated that 0.25 mg/kg scopolamine (SCOP) selectively increased proactive interference (PI) from stored odor memories during learning. In the present study, rats with bilateral cholinergic lesions limited to the horizontal limb of the diagonal band of Broca, made with 192 IgG-saporin, were not impaired in acquiring the same olfactory discrimination task relative to control rats. Rats with bilateral 192 IgG-saporin lesions to all basal forebrain cholinergic nuclei (BF) also showed no impairment in acquisition of this task. However, the BF-saporin rats were hypersensitive to oxotremorine-induced hypothermia and demonstrated an increased sensitivity to PI following a low dose of SCOP (0.125 mg/kg) relative to control rats. The results suggest that weaker cholinergic modulation after cholinergic BF lesions makes the system more sensitive to PI during blockade of the remaining cholinergic elements.


Subject(s)
Association Learning/physiology , Cholinergic Fibers/physiology , Mental Recall/physiology , Proactive Inhibition , Prosencephalon/physiology , Smell/physiology , Animals , Body Temperature Regulation/physiology , Brain Mapping , Diagonal Band of Broca/physiology , Dominance, Cerebral/physiology , Male , Rats , Rats, Sprague-Dawley , Retention, Psychology/physiology
10.
Network ; 11(3): 169-90, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11014667

ABSTRACT

Neurons in inferior temporal (IT) cortex exhibit selectivity for complex visual stimuli and can maintain activity during the delay following the presentation of a stimulus in delayed match to sample tasks. Experimental work in awake monkeys has shown that the responses of IT neurons decline during presentation of stimuli which have been seen recently (within the past few seconds). In addition, experiments have found that the responses of IT neurons to visual stimuli also decline as the stimuli become familiar, independent of recency. Here a biologically based neural network simulation is used to model these effects primarily through two processes. The recency effects are caused by adaptation due to a calcium-dependent potassium current, and the familiarity effects are caused by competitive self-organization of modifiable feedforward synapses terminating on IT cortex neurons.


Subject(s)
Artificial Intelligence , Neural Networks, Computer , Neurons/physiology , Temporal Lobe/physiology , Acetylcholine/physiology , Algorithms , Arousal/physiology , Calcium/physiology , Humans , Interneurons/physiology , Models, Neurological , Parasympathetic Nervous System/cytology , Parasympathetic Nervous System/physiology , Potassium Channels/physiology , Synapses/physiology , Temporal Lobe/cytology
11.
Ann N Y Acad Sci ; 911: 418-46, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10911889

ABSTRACT

Computational modeling provides a means for linking the physiological and anatomical characteristics of entorhinal cortex at a cellular level to the functional role of this region in behavior. We have developed detailed simulations of entorhinal cortical neurons and networks, with an emphasis on the role of acetylcholine in entorhinal cortical function. Computational modeling suggests that when acetylcholine levels are high, this sets appropriate dynamics for the storage of stimuli during performance of delayed matching tasks. In particular, acetylcholine activates a calcium-sensitive nonspecific cation current which provides an intrinsic cellular mechanism which could maintain neuronal activity across a delay period. Simulations demonstrate how this phenomena could underlie entorhinal cortex delay activity as described in previous unit recordings. Acetylcholine also induces theta rhythm oscillations which may be appropriate for timing of afferent input to be encoded in hippocampus and for extraction of individual stored sequences from multiple stored sequences. Lower levels of acetylcholine may allow sharp wave dynamics which can reactivate associations encoded in hippocampus and drive the formation of additional traces in hippocampus and entorhinal cortex during consolidation.


Subject(s)
Entorhinal Cortex/physiology , Models, Neurological , Acetylcholine/physiology , Animals , Cholinergic Agents/pharmacology , Hippocampus/physiology , Humans , Memory/drug effects , Memory/physiology , Theta Rhythm
12.
J Neurophysiol ; 83(5): 2562-79, 2000 May.
Article in English | MEDLINE | ID: mdl-10805658

ABSTRACT

Various subsets of brain neurons express a hyperpolarization-activated inward current (I(h)) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na(+)-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I(h) because it was resistant to extracellular Ba(2+), sensitive to Cs(+), completely and selectively abolished by ZD7288, and carried by both Na(+) and K(+) ions. I(h) in the SCs had an activation threshold and reversal potential at approximately -45 and -20 mV, respectively. Its half-activation voltage was -77 mV. Importantly, bath perfusion with ZD7288, but not Ba(2+), gradually and completely abolished the subthreshold oscillations, thus directly implicating I(h) in their generation. Using experimentally derived biophysical parameters for I(h) and the low-threshold persistent Na(+) current (I(NaP)) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I(NaP) and I(h) can sustain persistent subthreshold oscillations in SCs. I(NaP) and I(h) operate in a "push-pull" fashion where the delay in the activation/deactivation of I(h) gives rise to the oscillatory process.


Subject(s)
Biological Clocks/physiology , Entorhinal Cortex/physiology , Neurons/physiology , Animals , Barium/pharmacology , Buffers , Cardiovascular Agents/pharmacology , Cesium/pharmacology , Dose-Response Relationship, Drug , Electric Stimulation , Entorhinal Cortex/drug effects , In Vitro Techniques , Ion Transport/drug effects , Ion Transport/physiology , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Memory/physiology , Models, Neurological , Neurons/drug effects , Patch-Clamp Techniques , Pyrimidines/pharmacology , Rats , Rats, Long-Evans , Tetrodotoxin/pharmacology , Time Factors
13.
J Neurophysiol ; 83(4): 2138-44, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10758123

ABSTRACT

Cholinergic and GABAergic neurons projecting to the hippocampus fire with specific phase relations to theta rhythm oscillations in the electroencephalogram (EEG). To determine if this phasic input has an impact on synaptic transmission within the hippocampus, we recorded evoked population excitatory postsynaptic potential (EPSPs) during different phases of theta rhythm by using techniques similar to those described in Rudell and Fox. Synaptic potentials elicited by stimulation of region CA3 of the contralateral hippocampus were recorded in region CA1 and CA3. In these experiments, the initial slope of evoked potentials showed a change in magnitude during different phases of the theta rhythm recorded in the dentate fissure, with individual trials showing an average of 9.5% change in slope of potentials, and the average across all experiments showing a change of 7.8%. Evoked potentials were maximal 18 degrees after the positive peak of the dentate fissure theta EEG. These potentials were also smaller by 18.2% during theta as opposed to non-theta states. Phasic changes in modulation of synaptic transmission could contribute to phase precession of hippocampal place cells and could enhance storage of new sequences of activity as demonstrated by computational models.


Subject(s)
Dentate Gyrus/physiology , Pyramidal Cells/physiology , Synapses/physiology , Theta Rhythm , Anesthesia , Animals , Consciousness , Dentate Gyrus/cytology , Electric Stimulation , Evoked Potentials/physiology , Male , Microelectrodes , Rats , Rats, Sprague-Dawley
14.
Neurosci Lett ; 282(3): 157-60, 2000 Mar 24.
Article in English | MEDLINE | ID: mdl-10717415

ABSTRACT

Previously published theoretical models of olfactory processing suggest that cholinergic modulatory inputs to the olfactory system should be regulated by neural activity in the olfactory bulb. We tested these predictions using in vivo electrophysiology in rats. We show that the activity of approximately 20% of neurons recorded in the horizontal limb of the diagonal band of Broca (HDB), which is the source of cholinergic projections to the olfactory system, can be modulated by electrical stimulation of either the lateral olfactory tract or the cell body layer of piriform cortex. These data suggest a possible physiological pathway for the proposed regulation of neural activity in the HDB by activity in the olfactory bulb or cortex.


Subject(s)
Diagonal Band of Broca/physiology , Olfactory Pathways/physiology , Animals , Diagonal Band of Broca/cytology , Electric Stimulation , Male , Neurons/physiology , Olfactory Bulb/physiology , Rats , Rats, Sprague-Dawley
15.
Behav Neurosci ; 114(1): 32-41, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10718260

ABSTRACT

Previous electrophysiological studies and computational modeling suggest the hypothesis that cholinergic neuromodulation may reduce olfactory associative interference during learning (M. E. Hasselmo, B. P. Anderson, & J. M. Bower, 1992; M. E. Hasselmo & J. M. Bower, 1993). These results provide behavioral evidence supporting this hypothesis. A simultaneous discrimination task required learning a baseline odor pair (A+B-) and then, under the influence of scopolamine, a novel odor pair (A-C+) with an overlapping component (A) versus a novel odor pair (D+E-) with no overlapping component. As predicted by the model, rats that received scopolamine (0.50 and 0.25 mg/kg) were more impaired at acquiring overlapping than nonoverlapping odor pairs relative to their performance under normal saline or methylscopolamine. These results support the prediction that the physiological effects of acetylcholine can reduce interference between stored odor memories during associative learning.


Subject(s)
Association Learning/drug effects , Mental Recall/drug effects , Muscarinic Antagonists/pharmacology , Proactive Inhibition , Receptors, Muscarinic/drug effects , Scopolamine/pharmacology , Smell/drug effects , Animals , Dose-Response Relationship, Drug , Male , N-Methylscopolamine/pharmacology , Rats , Rats, Sprague-Dawley , Retention, Psychology/drug effects , Synaptic Transmission/drug effects
16.
Arch Gen Psychiatry ; 56(11): 1001-5, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10565499

ABSTRACT

BACKGROUND: Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. METHODS: Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. RESULTS: Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. CONCLUSIONS: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.


Subject(s)
Auditory Perception/physiology , Electroencephalography/statistics & numerical data , Evoked Potentials, Auditory/physiology , Schizophrenia/diagnosis , Acoustic Stimulation , Adult , Auditory Pathways/physiology , Cortical Synchronization/statistics & numerical data , Humans , Male , Middle Aged , Receptors, GABA/physiology , Receptors, N-Methyl-D-Aspartate/physiology , Schizophrenia/physiopathology
18.
Physiol Behav ; 66(3): 497-502, 1999 May.
Article in English | MEDLINE | ID: mdl-10357440

ABSTRACT

For a better understanding of the encoding of odor quality in the olfactory system, it is critical to determine how electrophysiological responses to odorants are reflected in the behavioral responses to these odorants. In this article, we use a simple behavioral paradigm to show that the behavioral responses to similar odorants can be predicted from the electrophysiological responses of neurons in the olfactory bulb. Carbon chain length in aliphatic aldehydes has been used as a model for graded similarity among odorants. Recent electrophysiological experiments have shown that mitral cells in the rabbit olfactory bulb respond with similar response patterns to aliphatic aldehydes of similar chain length. On average, mitral cells responded with increased spiking activity to stimulation with two to three different aldehydes of neighboring chain length. We here show that the perception of these odorants can be predicted from the electrophysiological responses: rats that are conditioned to a given aldehyde generalize to aldehydes with one to two carbon differences in chain length from the conditioned aldehyde. When asked to discriminate between aldehydes of different chain lengths, rats learned to discriminate between any two odorants, but the rate of acquisition depended on the degree of similarity between the two odorants.


Subject(s)
Aldehydes/pharmacology , Discrimination, Psychological/physiology , Generalization, Stimulus/physiology , Odorants , Smell/physiology , Aldehydes/chemistry , Analysis of Variance , Animals , Appetitive Behavior/physiology , Conditioning, Psychological/physiology , Male , Olfactory Bulb/physiology , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship
19.
J Neurophysiol ; 81(6): 2737-42, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10368393

ABSTRACT

Electrical stimulation of the horizontal limb of the diagonal band of Broca (HDB) was coupled with recording of evoked potentials in the piriform cortex. Stimulation of the HDB caused an enhancement of the late, disynaptic component of the evoked potential elicited by stimulation of the lateral olfactory tract but caused a suppression of the synaptic potential elicited by stimulation of the posterior piriform cortex. The muscarinic antagonist scopolamine blocked both effects of HDB stimulation. The enhancement of disynaptic potentials could be due to cholinergic depolarization of pyramidal cells, whereas the suppression of potentials evoked by posterior piriform stimulation could be due to presynaptic inhibition of intrinsic fiber synaptic transmission by acetylcholine.


Subject(s)
Entorhinal Cortex/physiology , Frontal Lobe/physiology , Olfactory Pathways/physiology , Animals , Electric Stimulation , Excitatory Postsynaptic Potentials/physiology , Male , Muscarinic Antagonists/pharmacology , Olfactory Bulb/physiology , Parasympathetic Nervous System/physiology , Pyramidal Cells/drug effects , Rats , Rats, Sprague-Dawley , Scopolamine/pharmacology , Synaptic Transmission/physiology
20.
J Neurophysiol ; 81(5): 2103-18, 1999 May.
Article in English | MEDLINE | ID: mdl-10322052

ABSTRACT

Modulation of inhibitory synaptic potentials in the piriform cortex. Intracellular recordings from pyramidal neurons in brain slice preparations of the piriform cortex were used to test results from a computational model about the effects of cholinergic agonists on inhibitory synaptic potentials induced by stimulation of afferent fibers in layer Ia and association/intrinsic fibers in layer Ib. A simple model of piriform cortex as an associative memory was used to analyze how suppression of inhibitory synaptic transmission influenced performance of the network. Levels of suppression of excitatory synaptic transmission were set at levels determined in previous experimental work. Levels of suppression of inhibitory synaptic transmission were then systematically varied within the model. This modeling work demonstrated that suppression of inhibitory synaptic transmission in layer Ib should be stronger than suppression of inhibitory synaptic transmission in layer Ia to keep activity levels high enough for effective storage. Experimental data showed that perfusion of the cholinergic agonist carbachol caused a significant suppression of inhibitory postsynaptic potentials (IPSPs) in the pyramidal neurons that were induced by stimulation of layer Ib, with a weaker effect on IPSPs induced by stimulation of layer Ia. As previously described, carbachol also selectively suppressed excitatory postsynaptic potentials (EPSPs) elicited by intrinsic but not afferent fiber stimulation. The decrease in amplitude of IPSPs induced by layer Ib stimulation did not appear to be directly related to the decrease in EPSP amplitude induced by layer Ib stimulation. The stimulation necessary to induce neuronal firing with layer Ia stimulation was reduced in the presence of carbachol, whereas that necessary to induce neuronal firing with layer Ib stimulation was increased, despite the depolarization of resting membrane potential. Thus physiological data on cholinergic modulation of inhibitory synaptic potentials in the piriform cortex is compatible with the functional requirements determined from computational models of piriform cortex associative memory function.


Subject(s)
Models, Neurological , Neural Inhibition/physiology , Olfactory Pathways/physiology , Synaptic Transmission/physiology , Animals , Carbachol/pharmacology , Cholinergic Agonists/pharmacology , Differential Threshold/physiology , Electrophysiology , Feedback , Female , In Vitro Techniques , Interneurons/physiology , Olfactory Pathways/cytology , Rats , Rats, Sprague-Dawley , Synaptic Transmission/drug effects
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