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M E Hasselmo

Publications and source records attributed to M E Hasselmo.

9 recordsLinked to original sources

Cholinergic suppression specific to intrinsic not afferent fiber synapses in rat piriform (olfactory) cortex.

1. Differences in the cholinergic suppression of afferent and intrinsic fiber synaptic transmission were studied in the rat piriform cortex. Extracellular and intracellular recording techniques were applied in an in vitro transverse slice preparation. Afferent and intrinsic fiber systems were differentially stimulated with electrodes placed in layer Ia or layer Ib, respectively. Synaptic responses were monitored in the presence of cholinergic agonists and antagonists. 2. Afferent and intrinsic fiber synaptic potentials measured extracellularly showed large differences in sensitivity to micromolar concentrations of the cholinergic agonists carbachol or (+/-)-muscarine, or to acetylcholine combined with neostigmine. Intrinsic fiber synaptic responses in layer Ib were strongly reduced in the presence of cholinergic agonists, whereas afferent fiber synaptic responses in layer Ia were largely unaffected. At a concentration of 100 microM, all three agonists caused a greater than 60% decrease in the height of the intrinsic fiber synaptic potential but less than 15% reduction in the afferent fiber synaptic potential. 3. Intracellular recordings confirmed that the cholinergic agonist carbachol selectively suppresses intrinsic fiber synaptic potentials but not afferent fiber synaptic potentials recorded from the same pyramidal cell. 4. Dose-response curves to carbachol were obtained for both fiber systems using extracellular recording of evoked field potentials. Carbachol suppressed intrinsic fiber synaptic potentials with a coefficient of dissociation (KD) estimated at 2.9 microM and an inhibitory concentration for 50% response estimated at 6.6 microM. 5. Carbachol produced a proportionately greater suppression of the first pulse than the second pulse of a pulse pair. This increase in the level of facilitation accompanying suppression suggests a presynaptic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways

Cholinergic modulation of cortical associative memory function.

1. The effect of cholinergic modulation on associative memory function was studied in a computational model based on the physiology and anatomic structure of piriform cortex. Both the cholinergic suppression of intrinsic fiber synaptic transmission and the cholinergic changes in postsynaptic excitability described in the companion paper were examined. 2. Distributed input patterns representing odors were stored in the model with the use of a synaptic modification rule dependent on pre- and postsynaptic activity (i.e., Hebbian). Associative recall of these patterns was tested by presenting the model with degraded versions of the learned patterns and testing whether these degraded patterns evoked the same network response as the full learned input pattern. Storage was evaluated with the use of a performance measure designed to reflect how well degraded input patterns could be recognized as a particular learned input pattern. 3. When memory function was evaluated with a selective cholinergic suppression of intrinsic fiber synaptic transmission during learning, associative memory performance was greatly enhanced. Cholinergic suppression during learning prevents previously stored patterns from interfering with the storage of new patterns. 4. When memory function was evaluated with a cholinergic mediated enhancement in cell excitability during learning, the speed of learning increased, but so did the decay in performance due to interference during learning. 5. When suppression of intrinsic fiber synaptic transmission was coupled with an increase in cell excitability, the best memory performance was obtained. 6. These results provide a possible theoretical framework for linking the neuropharmacological effects of acetylcholine to behavioral evidence for a role of acetylcholine in memory function. This could help describe how memory deficits might arise from cholinergic dysfunction in diseases such as Alzheimer's dementia.

Association

Selective suppression of afferent but not intrinsic fiber synaptic transmission by 2-amino-4-phosphonobutyric acid (AP4) in piriform cortex.

Differences in the glutaminergic modulation of afferent and intrinsic fiber synaptic transmission in piriform (olfactory) cortex were investigated using extracellular and intracellular recording techniques in a transverse slice preparation. 2-Amino-4-phosphonobutyric acid (AP4) strongly suppressed synaptic potentials evoked by afferent fiber stimulation in layer 1a, while having a much weaker effect on synaptic potentials evoked by intrinsic fiber stimulation in layer 1b. Both the racemic mixture and L-(+)-enantiomer of AP4 showed this differential effect. Suppression of afferent fiber synaptic potentials was accompanied by an increase in paired pulse facilitation, suggesting a pre-synaptic mechanism, while intrinsic fiber synaptic potentials showed little change in facilitation. Previous work has shown that cholinergic modulation in piriform cortex appears selective for intrinsic fiber synapses. The present data describes a pre-synaptic glutaminergic modulation complementary to the cholinergic modulation.

Afferent Pathways

Afferent and association fiber differences in short-term potentiation in piriform (olfactory) cortex of the rat.

1. The effects of low-frequency stimulus trains on synaptically evoked responses in piriform cortex pyramidal cells were studied by the use of intracellular recording techniques in an in vitro slice preparation. Afferent and association fiber systems were differentially stimulated with electrodes placed in layer 1a or layer 1b, respectively. To quantify synapse modifiability, the heights of postsynaptic potentials (PSPs) elicited by paired-pulse stimulation (100-ms interval) were averaged over a 50-s period before and after a set of 10 stimulus trains (10 pulses each, 20 Hz, 5-s interpulse interval). 2. Afferent and association fibers showed consistent differences in their response to stimulation during the period lasting from approximately 10 to 200 s after presentation of trains. During this time period, the responses to stimulation of association fibers in layer 1b displayed a short-term potentiation, which over the 10 posttrain trials, produced an average increase in PSP height of 23.2 +/- 3.7% (mean +/- SE). On the other hand, responses to layer 1a stimulation showed an average depression of 10.9 +/- 3.6%. Layer 1b potentiation decayed with time constant roughly estimated at 79 s. Layer 1b potentiation appeared even at very low stimulus voltages and after local association fiber input had been cut, suggesting that it was largely a monosynaptic effect. 3. In the period immediately after train presentations, responses evoked by both layers showed a short-term augmentation with a time constant around 3 s. In layer 1a, this augmentation was superimposed on a depression with slow recovery. At longer times after train presentation (greater than 5 min), 2 cells out of 46 showed changes (increases) in synaptic efficacy in response to layer 1b stimulation. 4. In the current experiments both layers 1a and 1b showed statistically significant facilitation before the presentation of stimulus trains. However, layer 1b facilitation decreased from 22.7 +/- 3.5% to a statistically insignificant 3.9 +/- 3.3% after the presentation of trains, whereas layer 1a facilitation remained at a statistically significant level of 23.1 +/- 5.7%. 5. These experiments show that pyramidal cell responses to stimulation of the afferent and association fiber systems are affected differently by the previous presentation of trains of stimuli. This suggests that mechanisms of synaptic modification may differ between the afferent and intrinsic association synaptic projections onto single pyramidal cells in olfactory cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The role of expression and identity in the face-selective responses of neurons in the temporal visual cortex of the monkey.

Neurophysiological studies have shown that some neurons in the cortex in the superior temporal sulcus and the inferior temporal gyrus of macaque monkeys respond to faces. To determine if facial factors such as expression and identity are encoded independently by face-responsive neurons, 45 neurons were tested on a stimulus set depicting 3 monkeys with 3 expressions each. As tested on a two-way ANOVA, 15 neurons showed response differences to different identities independently of expression, and 9 neurons showed responses to different expressions independently of identity. Three neurons showed significant effects of both factors. Six of the neurons with responses related to expression responded primarily to calm faces, while 2 responded primarily to threat faces. Of a further set of 31 neurons tested on pairs of different expressions, 6 showed strong responses to open-mouth fear or threat expressions, while 2 showed stronger responses to calm faces than threat expressions. Neurons responsive to expression were found primarily in the cortex in the superior temporal sulcus, while neurons responsive to identity were found primarily in the inferior temporal gyrus. The difference in anatomical distribution was statistically significant. This supports the possibility that specific impairments of the recognition of the identity of a face and of its expression in man are due to damage to or disconnection of separate neuronal substrates.

Animals

Object-centered encoding by face-selective neurons in the cortex in the superior temporal sulcus of the monkey.

Neurophysiological studies have shown that some neurons in the cortex in the superior temporal sulcus and in the inferior temporal cortex respond to faces. To determine if some face responsive neurons encode stimuli in an object-centered coordinate system rather than a viewer-centered coordinate system, a large number of neurons were tested for sensitivity to head movement in 3 macaque monkeys. Ten neurons responded only when a head undergoing rotatory movements was shown. All of these responded to a particular movement independently of the orientation of the moving head in relation to the viewer, maintaining specificity even when the moving head was inverted or shown from the back, thereby reversing viewer-centered movement vectors. This was taken as evidence that the movement was encoded in object-centered coordinates. In tests of whether there are neurons in this area which respond differently to the faces of different individuals relatively independently of viewing angle, it was found that a further 18 neurons responded more to one static face than another across different views. However, for 16 of these 18 cells there was still some modulation of the neuronal response with viewing angle. These 16 neurons thus did not respond perfectly in relation to the object shown independently of viewing angle, and may represent an intermediate stage between a viewer-centered and an object-centered representation. In the same area as these neurons, other cells were found which responded on the basis of viewer-centered coordinates. These neurophysiological findings provide evidence that some neurons in the inferior temporal visual cortex respond to faces (or heads) on the basis of object-centered coordinates, and that others have responses which are intermediate between object-centered and viewer-centered representations. The results are consistent with the hypothesis that object-centered representations are built in the inferior temporal visual cortex.

Animals

The effect of learning on the face selective responses of neurons in the cortex in the superior temporal sulcus of the monkey.

Neurophysiological studies have shown that some neurons in the cortex in the superior temporal sulcus and the inferior temporal gyrus of macaque monkeys respond to faces. These neurons provided a consistently identifiable substrate with which studies of the storage of visual information were performed. To determine whether face responsive neurons change how much they respond to different novel faces as they become familiar, neurons were tested with two experimental designs. In the first experiment, 22 neurons were tested on their responsiveness to the different members of a large set of novel faces as the set was presented repeatedly until the faces became familiar. 6 neurons altered the relative degree to which they responded to the different members of the set between the first two presentations and subsequent presentations. In a control condition, only 1 out of 17 neurons showed a significant response difference between the first two presentations and subsequent presentations when the experiment started with faces which were already familiar to the monkey. In the second experiment, 26 neurons were tested on their responsiveness to the different members of a set of familiar faces before and after the addition of a novel face to the set. 5 neurons altered the relative degree in which they responded to the different members of the set of familiar faces after addition of a novel face. It is suggested that these changes in neuronal responsiveness to different stimuli reflect the setting up of an ensemble encoded representation of face stimuli. This alteration of neuronal responsiveness as novel faces become familiar suggests that face responsive neurons may store information useful in visual recognition. In addition to this relatively long-term alteration of relative neuronal responsiveness to different stimuli, it was found that a large number of cells showed a higher mean response to the first presentation of a set of novel faces than to subsequent presentations of the faces. However, the response to the first presentation of a set of familiar faces was also higher than to subsequent presentations in that sequence. This pattern indicates a short term recency effect in the response of these neurons to visual stimuli which is similar to that previously reported (Baylis and Rolls 1987).

Animals

The responses of neurons in the cortex in the superior temporal sulcus of the monkey to band-pass spatial frequency filtered faces.

There are neurons in the cortex in the anterior part of the superior temporal sulcus of the macaque monkey with visual responses which would be useful for face recognition (Rolls, 1984; Baylis et al., 1985). To analyze further the information which leads them to respond, their responses were measured to parametrically filtered stimuli. The responses of 48 such single neurons were measured to faces which were digitized and were bandpass spatial frequency filtered. The octave width bands were 2-4, 4-8, 8-16, 16-32, 32-64 and 64-128 cycles per image. It was found that the neurons could respond well to single octaves of the spatial frequencies normally present in faces, that the most effective bands were 4-8, 8-16 and 16-32 cycles per face (cpf), and that the bands 2-4 and 32-64 cpf were partly effective. In investigations of whether the responses of the neurons to an unfiltered face, and to low-pass and high-pass filtered images could be predicted by linear addition of their responses to each of the octave bands shown separately, it was found that the majority of the neurons were non-linear, and responded much less than predicted. It was also shown that this occurred even when the contrast was reduced to 0.25 of that normally present in a face, so that the result was not due just to a ceiling effect of the maximum firing rate. These results help to define parametrically the aspects of the information normally present in a face which are sufficient to produce responses of these neurons to them, and show that linear operations cannot account for information processing in this part of the visual system.

Action Potentials