CiteULike: Tag tan

Development of plasma etching process for sub-50 nm TaN gate

Vladimir Bliznetsov — 2008-05-21T06:20:00-00:00

Thin Solid Films, Vol. 504, No. 1-2. (10 May 2006), pp. 140-144.

TaN has been identified as a possible candidate to replace polysilicon for sub-50 nm gate CMOS transistors. However, TaN gate etching in CD (critical dimensions) range below 100 nm presents a great challenge and not much information is available in this area. Using thin layer of SiO2 as a hard mask, TaN etching was evaluated in DPS (decoupled plasma source) etcher with four gas chemistries: Cl2, Cl2/BCl3/Ar, Cl2/BCl3, and Cl2/Ar. Due to lesser CD gain and higher selectivity to gate dielectrics, Cl2/Ar was chosen for further optimization by DOE. Based on the analysis of the effects of input parameters on the etch responses, we developed a two-step etch process with sub-50 nm minimal CD, profile close to vertical, and capability to stop on 5 nm HfAlO high-k dielectric. 60-nm gate transistors with TaN-HfAlO gate stack (equivalent oxide thickness of 2.5 nm) were fabricated with reasonably low gate leakage of 10- 2 A/cm2 at gate bias of 1 V and absence of polysilicon depletion effect.

Investigation of etching properties of metal nitride/high-k gate stacks using inductively coupled plasma

Wan Hwang — 2006-02-17T15:42:03-00:00

Vol. 23, No. 4. (2005), pp. 964-970.

Etching properties of metal nitrides (TaN, TiN, and HfN)/high dielectric constant material (HfO2) gate stacks in Cl2 and HBr were investigated using inductively coupled plasma. The linear dependence of etch rates on the square root of bias voltage indicates the dominance of ion-induced etch mechanism of the metal nitrides. This phenomenon is well explained by internal binding energy of substrate, evaporation temperature, and Gibb's free energy (Gf[degree]" align="middle">) of formation of byproducts. The addition of O2 in Cl2 and HBr decreased etch rates of the metal nitrides and HfO2; however, for O2 concentration lower than 1.5% in Cl2, a slight increase in etch rates of the metal nitrides was observed. X-ray photoelectron spectroscopy revealed that residues remain more on the sidewalls of gate stacks than the bottom of spaces between gates. The addition of O2 and the use of a SiO2 mask to increase etch selectivity of metal nitrides with respect to high-k dielectric increased surface roughness and formed micromasks on the etched surface. The optical emission signals from N, Cl, and Ta–Cl byproducts were sensitive enough to control the etch endpoints of the TaN/HfO2 stack structures. ©2005 American Vacuum Society

Physical and electrical properties of Ta--N, Mo--N, and W--N electrodes on HfO[sub 2] high-k gate dielectric

Jiang Lu — 2008-05-21T06:08:07-00:00

Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures, Vol. 24, No. 1. (2006), pp. 349-357.

The influence of various types of metal nitride gate electrodes, i.e., tantalum nitride, molybdenum nitride, and tungsten nitride, on electrical characteristics of metal-oxide-semiconductor capacitors with hafnium oxide as the gate dielectric material has been studied. The result shows that both the physical and electrical properties of the high-k gate stack are influenced by the gate electrode materials and the post-metal-annealing temperature. Both the physical thickness and equivalent oxide thickness of the gate stack increased after the high-temperature N2 annealing step. The leakage current density decreased with the increase of the annealing temperature from 600 to 800 °C. The work functions of these metal nitride electrodes decreased with the annealing temperature due to the variance of microstructure and chemical composition, as indicated by x-ray diffraction and second-ion-mass spectroscopy data. These metal nitride electrodes are suitable for n-channel metal-oxide-semiconductor device applications after 800 °C N2 annealing because their work functions are between 4.05 and 4.25 eV. The interface state density and oxide trap density of the high-k gate stack were also reduced by the high-temperature N2 annealing step. ©2006 American Vacuum Society

A network representation of response probability in the striatum.

PM Blazquez — 2006-05-25T12:26:25-00:00

Neuron, Vol. 33, No. 6. (14 March 2002), pp. 973-982.

The striatum of the basal ganglia is considered a key structure in the learning circuitry of the brain. To analyze neural signals that underlie striatal plasticity, we recorded from an identifiable class of striatal interneurons as macaque monkeys underwent training in a range of conditioning and non-associative learning paradigms, and recorded eyeblink electromyographs as the measure of behavioral response. We found that the responses of these striatal interneurons were modifiable under all training conditions and that their population responses were tightly correlated with the probability that a given stimulus would evoke a behavioral response. Such a network signal, proportional to current response probability, could be crucial to the learning and decision functions of the basal ganglia.

Re-emergence of striatal cholinergic interneurons in movement disorders

Antonio Pisani — 2007-10-06T11:16:25-00:00

Trends in Neurosciences, Vol. In Press, Corrected Proof

Twenty years ago, striatal cholinergic neurons were central figures in models of basal ganglia function. But since then, they have receded in importance. Recent studies are likely to lead to their re-emergence in our thinking. Cholinergic interneurons have been implicated as key players in the induction of synaptic plasticity and motor learning, as well as in motor dysfunction. In Parkinson's disease and dystonia, diminished striatal dopaminergic signalling leads to increased release of acetylcholine by interneurons, distorting network function and inducing structural changes that undoubtedly contribute to the symptoms. By contrast, in Huntington's disease and progressive supranuclear palsy, there is a fall in striatal cholinergic markers. This review gives an overview of these recent experimental and clinical studies, placing them within the context of the pathogenesis of movement disorders.

The mechanism of intrinsic amplification of hyperpolarizations and spontaneous bursting in striatal cholinergic interneurons.

CJ Wilson — 2005-09-13T13:19:00-00:00

Neuron, Vol. 45, No. 4. (17 February 2005), pp. 575-585.

Striatal cholinergic interneurons pause their ongoing firing in response to sensory stimuli that have acquired meaning as a signal for learned behavior. In slices, these cells exhibit both spontaneous activity patterns and spontaneous pauses very similar to those seen in vivo. The mechanisms responsible for ongoing firing and spontaneous pauses were studied in striatal slices using perforated patch recordings. All hyperpolarizations, whether spontaneous or generated by current injection, were amplified and shaped by two hyperpolarization-activated currents. Hyperpolarization onsets were regeneratively amplified by a potassium current (KIR) whose activation promoted further hyperpolarization. The termination of hyperpolarizations was controlled by a time-dependent nonspecific cation current (HCN). The duration and even the sizes of spontaneous and driven hyperpolarizations and pauses in spontaneous activity in cholinergic interneurons are largely autonomous properties of the neuron, rather than reflections of characteristics of the input eliciting the response.

Cholinergic interneuron characteristics and nicotinic properties in the striatum.

FM Zhou — 2008-05-21T09:01:07-00:00

Journal of neurobiology, Vol. 53, No. 4. (December 2002), pp. 590-605.

The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.

Endogenous Serotonin Excites Striatal Cholinergic Interneurons via the Activation of 5-HT 2C, 5-HT6, and 5-HT7 Serotonin Receptors: Implications for Extrapyramidal Side Effects of Serotonin Reuptake Inhibitors

Paola Bonsi — 2007-01-03T21:16:49-00:00

Neuropsychopharmacology, Vol. aop, No. current.

Meaningful silences: how dopamine listens to the ACh pause.

Stephanie J Cragg — 2006-02-26T18:42:47-00:00

Trends Neurosci (26 January 2006)

Mesostriatal dopaminergic neurons (DANs) and striatal cholinergic neurons (tonically active neurons, TANs) participate in signalling the behavioural or reward-related significance of stimuli in the environment. An antagonistic balance between dopamine (DA) and ACh is well known to regulate postsynaptic signal integration in the striatum. Recent findings have revealed additional presynaptic ACh-DA interactions of previously unappreciated sophistication. Striatal ACh acts presynaptically to polarize powerfully how opposing DAN activities are transduced into DA release. Furthermore, characteristic reward-related activities of TANs and DANs are temporally coincident but differently variant with reward probability. Reward-related DA signals could therefore be governed by the concomitant activity in TANs. This article discusses the dynamic implications for DA signalling when these phenomena act in concert. TAN pauses might powerfully enhance the contrast, or salience, of DA signals offered by reward-related bursts, and even by reward omission-related pauses, in DANs. Through such mechanisms, TAN-DAN interactions would be functionally cooperative.

Leading tonically active neurons of the striatum from reward detection to context recognition

Paul Apicella — 2007-04-12T13:30:26-00:00

Trends in Neurosciences, Vol. In Press, Corrected Proof

Tonically active neurons (TANs) in the primate striatum, which are presumed to be cholinergic interneurons, carry signals that are traditionally considered to be important for reward-related learning. Recent studies investigating the functional properties of TANs in behaving monkeys have shown that other factors beyond motivation can affect their responsiveness. There is now evidence that TAN responses reflect stimulus detection, movement control and recognition of a specific context, suggesting that these local circuit neurons contribute to different computations used in learning and action functions of the striatum. This is consistent with the view that TAN responses could represent an important component of the processes that are responsible for the ability to select the appropriate behavioral response to environmental events.

Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons.

G Morris — 2005-06-01T15:22:14-00:00

Neuron, Vol. 43, No. 1. (8 July 2004), pp. 133-143.

Midbrain dopamine and striatal tonically active neurons (TANs, presumed acetylcholine interneurons) signal behavioral significance of environmental events. Since striatal dopamine and acetylcholine affect plasticity of cortico-striatal transmission and are both crucial to learning, they may serve as teachers in the basal ganglia circuits. We recorded from both neuronal populations in monkeys performing a probabilistic instrumental conditioning task. Both neuronal types respond robustly to reward-related events. Although different events yielded responses with different latencies, the responses of the two populations coincided, indicating integration at the target level. Yet, while the dopamine neurons' response reflects mismatch between expectation and outcome in the positive domain, the TANs are invariant to reward predictability. Finally, TAN pairs are synchronized, compared to a minority of dopamine neuron pairs. We conclude that the striatal cholinergic and dopaminergic systems carry distinct messages by different means, which can be integrated differently to shape the basal ganglia responses to reward-related events.

Tonically active neurons in the striatum encode motivational contexts of action.

M Kimura — 2008-01-02T16:32:00-00:00

Brain Dev, Vol. 25 Suppl 1 (December 2003)

In order to achieve a goal, one procures immediately available rewards, escape from aversive events or endures absence of rewards. The neuronal substrate for these goal-directed actions includes the limbic system and the basal ganglia. In the basal ganglia, classes of projection neurons in the striatum show activity with motivational as well as sensorimotor properties, such as expectation of reward and task schedule for obtaining reward. Tonically active neurons (TANs), presumed cholinergic interneurons in the striatum, respond to reward-associated stimuli, evolve their activity through learning and respond also to aversive event-associated stimuli such as airpuff on the face. A recent study showed that responses to visual cues are less selective to whether the cue instructs reward or no reward. To address this paradox, we asked macaque monkeys to perform a set of visual reaction time tasks while expecting the reward, aversive event or absence of reward. We found that TANs respond to instruction stimuli associated with motivational outcomes but not to unassociated ones, and that they mostly differentiate associated instructions. We also found that the higher percentage of TANs in the caudate nucleus respond to stimuli associated with motivational outcomes than in the putamen, whereas the higher percentage of TANs in the putamen respond to GO signals than in the caudate nucleus especially for an action anticipating a reward. These findings suggest a distinct, pivotal role played by TANs in the caudate nucleus and putamen in encoding instructed motivational contexts for goal-directed action selection and learning in the striatum.

Implementation of high-k and metal gate materials for the 45 nm node and beyond: gate patterning development

S Beckx — 2006-02-17T15:33:53-00:00

Microelectronics and Reliability, Vol. 45, No. 5-6. ( 2005), pp. 1007-1011.

We report on gate patterning development for the 45 nm node and beyond. Both poly-Si and different metal gates in combination with medium-k and high-k dielectrics have been defined. Source/drain silicon recess has been characterized for different stacks, yielding optimised processes for all investigated. Using hardmask based etching allowed us to produce sub-20 nm poly-Si and metal gates. Implementation of advanced metal gate patterning in already developed multi-gate field effect transistors (MuGFET) devices has been demonstrated.

Neurons in the thalamic CM-Pf complex supply striatal neurons with information about behaviorally significant sensory events.

N Matsumoto — 2005-06-15T14:14:53-00:00

J Neurophysiol, Vol. 85, No. 2. (February 2001), pp. 960-976.

The projection from the thalamic centre médian-parafascicular (CM-Pf) complex to the caudate nucleus and putamen forms a massive striatal input system in primates. We examined the activity of 118 neurons in the CM and 62 neurons in the Pf nuclei of the thalamus and 310 tonically active neurons (TANs) in the striatum in awake behaving macaque monkeys and analyzed the effects of pharmacologic inactivation of the CM-Pf on the sensory responsiveness of the striatal TANs. A large proportion of CM and Pf neurons responded to visual (53%) and/or auditory beep (61%) or click (91%) stimuli presented in behavioral tasks, and many responded to unexpected auditory, visual, or somatosensory stimuli presented outside the task context. The neurons fell into two classes: those having short-latency facilitatory responses (SLF neurons, predominantly in the Pf) and those having long-latency facilitatory responses (LLF neurons, predominantly in the CM). Responses of both types of neuron appeared regardless of whether or not the sensory stimuli were associated with reward. These response characteristics of CM-Pf neurons sharply contrasted with those of TANs in the striatum, which under the same conditions responded preferentially to stimuli associated with reward. Many CM-Pf neurons responded to alerting stimuli such as unexpected handclaps and noises only for the first few times that they occurred; after that, the identical stimuli gradually became ineffective in evoking responses. Habituation of sensory responses was particularly common for the LLF neurons. Inactivation of neuronal activity in the CM and Pf by local infusion of the GABA(A) receptor agonist, muscimol, almost completely abolished the pause and rebound facilitatory responses of TANs in the striatum. Such injections also diminished behavioral responses to stimuli associated with reward. We suggest that neurons in the CM and Pf supply striatal neurons with information about behaviorally significant sensory events that can activate conditional responses of striatal neurons in combination with dopamine-mediated nigrostriatal inputs having motivational value.

Participation of the thalamic CM-Pf complex in attentional orienting.

T Minamimoto — 2005-06-15T14:13:51-00:00

J Neurophysiol, Vol. 87, No. 6. (June 2002), pp. 3090-3101.

The centre médian-parafascicular (CM-Pf) complex is located at the posterior intralaminar nuclei of the thalamus and forms part of the nonspecific thalamocortical projection system and the internal circuit of the basal ganglia. However, the functional roles of this complex remain to be fully elucidated. Here we have examined whether the CM-Pf complex is involved in the process of covert attention. We trained two macaque monkeys to perform a task in which a visual target stimulus for button release appeared at either the same location as the preceding visual instruction cue (a "validly cued target") or a location on the opposite side (an "invalidly cued target"). Reaction times (RTs) to a validly cued target were significantly shorter than those to an invalidly cued target, leading to a "validity effect" of about 20 ms. We recorded the activity of 97 neurons in the CM-Pf while the monkeys performed the attention task with the hand that was contralateral to the neuronal recording. Seventy CM-Pf neurons showed task-related activity after the appearance of either the instruction cue or the target stimulus: 33 neurons responded with a prominent short-latency facilitation (SLF), whereas 37 responded with a short-latency suppression followed by a long-latency facilitation (LLF). Most of the SLF neurons responded preferentially to a cue appearing on the contralateral side (76%) and to an invalidly cued target appearing on the contralateral side (61%). In contrast, LLF neurons showed a short-latency suppression after the cue stimulus, regardless of whether the cue appeared on the contra- or ipsilateral side (84%). Inactivating the CM-Pf complex by local injection (1 microl) of the GABA(A) receptor agonist muscimol (1-5 microg/microl) resulted in a significant increase in the RT to a validly cued target presented on the contra- but not the ipsilateral side. In contrast, inactivating the CM-Pf complex did not affect RTs to invalidly cued targets on either the contra- or the ipsilateral side. Thus the validity effect was abolished only on the contralateral side. We conclude that the CM-Pf complex plays a specific and essential role in the process of attentional orienting to external events occurring on the contralateral side, probably through the projection of primary outputs to the striatum, which is involved in the action-selection mechanisms of the basal ganglia.

Tonically active neurons in the primate caudate nucleus and putamen differentially encode instructed motivational outcomes of action.

H Yamada — 2005-10-14T16:57:57-00:00

J Neurosci, Vol. 24, No. 14. (7 April 2004), pp. 3500-3510.

To achieve a goal, animals procure immediately available rewards, escape from aversive events, or endure the absence of rewards. The neuronal substrates for these goal-directed actions include the limbic system and the basal ganglia. In the striatum, tonically active neurons (TANs), presumed cholinergic interneurons, were originally shown to respond to reward-associated stimuli and to evolve their activity through learning. Subsequent studies revealed that they also respond to aversive event-associated stimuli such as an airpuff on the face and that they are less selective to whether the stimuli instruct reward or no reward. To address this paradox, we designed a set of experiments in which macaque monkeys performed a set of visual reaction time tasks while expecting a reward, during escape from an aversive event, and in the absence of a reward. We found that TANs respond to instruction stimuli associated with motivational outcomes (312 of 390; 80%) but not to unassociated ones (51 of 390; 13%), and that they mostly differentiate associated instructions (217 of 312; 70%). We also found that a higher percentage of TANs in the caudate nucleus respond to stimuli associated with motivational outcomes (118 of 128; 92%) than in the putamen (194 of 262; 74%), whereas a higher percentage of TANs in the putamen respond to go signals for the lever release (112 of 262; 43%) than in the caudate nucleus (27 of 128; 21%), especially for an action expecting a reward. These findings suggest a distinct, pivotal role of TANs in the caudate nucleus and putamen in encoding instructed motivational contexts for goal-directed action planning and learning.

Influence of spatial information on responses of tonically active neurons in the monkey striatum.

S Ravel — 2006-05-24T01:20:27-00:00

J Neurophysiol, Vol. 95, No. 5. (May 2006), pp. 2975-2986.

Previous studies have demonstrated that tonically active neurons (TANs) in the primate striatum play an important role in the detection of rewarding events. However, the influence of the spatial features of stimuli or actions required to obtain reward remains unclear. Here, we examined the activity of TANs in the striatum of monkeys trained to make spatially directed movements elicited by visual stimuli presented ipsilaterally or contralaterally to the moving arm. Among 181 neurons responding to the trigger stimulus, 127 (70%) were nonselective for stimulus location and 54 (30%) responded to only one location of the stimulus. Most of the selective responses (63%) occurred when the stimulus was presented contralaterally to the moving arm. To examine whether TAN responses are related to the location of the stimulus or to the direction of the movement, we tested a subset of the trigger-responsive neurons (n = 44) in a condition that elicited reaching toward or away from the stimulus. By comparing TAN activity between the two conditions, we found that half of the responses can be interpreted as being related to the location of the stimulus, one quarter to the direction of movement, and one quarter to the context in which stimulus-movement combination occurs. These results demonstrate that TANs are not limited to motivational processing, but may play a role in the processing of spatial attributes of stimulus and/or movement as well. These response properties suggest that TANs are involved in the flexible shifting of motor responses during spatially directed behavior.

Dopamine receptor-mediated mechanisms involved in the expression of learned activity of primate striatal neurons.

K Watanabe — 2005-10-20T21:35:20-00:00

J Neurophysiol, Vol. 79, No. 5. (May 1998), pp. 2568-2580.

To understand the mechanisms by which basal ganglia neurons express acquired activities during and after behavioral learning, selective dopamine (DA) receptor antagonists were applied while recording the activity of striatal neurons in monkeys performing behavioral tasks. In experiment 1, a monkey was trained to associate a click sound with a drop of reward water. DA receptor antagonists were administered by micropressure using a stainless steel injection cannula (300 microm ID) through which a Teflon-coated tungsten wire for recording neuronal activity had been threaded. Responses to sound by tonically active neurons (TANs), a class of neurons in the primate striatum, were recorded through a tungsten wire electrode during the application of either D1- or D2-class DA receptor antagonists (total volume <1 microl, at a rate of 1 microl/5-10 min). Application of the D2-class antagonist, (-)-sulpiride (20 micrograms/microl, 58 mM, pH 6.8), abolished the responses of four of five TANs examined. In another five TANs, neither the D2-class antagonist nor the D1-class antagonists, SCH23390 (10 micrograms/microl, 31 mM, pH 5.7) or cis-flupenthixol (30 micrograms/microl, 59 mM, pH 6.6) significantly suppressed responses. In experiment 2, four- or five-barreled glass microelectrodes were inserted into the striatum. The central barrel was used for extracellular recording of activity of TANs. Each DA receptor antagonist was iontophoretically applied through one of the surrounding barrels. SCH23390 (10 mM, pH 4.5) and (-)-sulpiride (10 mM, pH 4.5) were used. The effects of iontophoresis of both D1- and D2-class antagonists were examined in 40 TANs. Of 40 TANs from which recordings were made, responses were suppressed exclusively by the D2-class antagonist in 19 TANs, exclusively by the D1-class antagonist in 3 TANs, and by both D1- and D2-class antagonists in 7 TANs. When 0.9% NaCl, saline, was applied by pressure (<1 microl) or by iontophoresis (<30 nA) as a control, neither the background discharge rates nor the responses of TANs were significantly influenced. Background discharge rate of TANs was also not affected by D1- or D2-class antagonists applied by either micropressure injection or iontophoresis. It was concluded that the nigrostriatal DA system enables TANs to express learned activity primarily through D2-class and partly through D1-class receptor-mediated mechanisms in the striatum.

Tonically active neurons in the primate striatum and their role in the processing of information about motivationally relevant events.

P Apicella — 2005-10-14T16:54:59-00:00

Eur J Neurosci, Vol. 16, No. 11. (December 2002), pp. 2017-2026.

Analysis of recordings of single neuronal activity in the striatum of monkeys engaged in behavioural tasks has shown that tonically active neurons (TANs) can be distinguished by their distinct spontaneous firing and functional properties. As TANs are assumed to be cholinergic interneurons, the study of their physiological characteristics allows us to gain an insight into the role of a particular type of local-circuit neuron in the processing of information at the striatal level. In monkeys performing various behavioural tasks, the change in the activity of TANs, unlike the diversity of task-related activations exhibited by the phasically active population of striatal neurons, involves a transient depression of the tonic firing related to environmental events of motivational significance. Such events include primary rewards and stimuli that have acquired a reward value during associative learning. These neurons also respond to an aversive air puff, indicating that their responsiveness is not restricted to appetitive conditions. Another striking feature of the TANs is that their responses can be modulated by predictions about stimulus timing. Temporal variations in event occurrence have been found to favour the responses of TANs, whereas the responses are diminished or abolished in the presence of external cues that predict the time at which events will occur. These data suggest that the TANs respond as do detectors of motivationally relevant events, but they also demonstrate that these neurons are influenced by predictive information based on past experience with a given temporal context. TANs represent a unique subset of striatal neurons that might serve a modulatory function, monitoring for temporal relationships between environmental events.

Responses of tonically active neurons in the monkey striatum discriminate between motivationally opposing stimuli.

S Ravel — 2005-10-20T21:23:48-00:00

J Neurosci, Vol. 23, No. 24. (17 September 2003), pp. 8489-8497.

The striatum is involved in the control of appetitively motivated behavior. We found previously that tonically active neurons (TANs) in the monkey striatum show discriminative responses to different stimuli that are appetitive or aversive. However, these differential responses may reflect the sensory qualities of the stimulus rather than its motivational value. In the present study, we sought to define more precisely the relationship between the particular aspect of the response of TANs and the motivational value of stimuli. For this purpose, three monkeys were presented with two types of aversive stimuli (loud sound and air puff) and one appetitive stimulus (fruit juice). In most instances, the TAN responses to the loud sound and the air puff were similar, in terms of response pattern and duration, whereas responses to the liquid reward showed distinct features. Using classical appetitive conditioning, we reversed the motivational value of a stimulus so that a previously aversive stimulus was now associatively paired with a reward and found that this manipulation selectively modifies the expression of TAN responses to the stimulus. These data indicate that the characteristics of neuronal responses undergo modifications when the valence of the stimulus is changed from aversive to appetitive during associative learning, suggesting that TANs may contribute to a form of stimulus encoding that is dependent on motivational attributes. The adaptation of TAN responses such as observed in the present study likewise reflects a neuronal system that adjusts to the motivational information about environmental events.

Role of tonically active neurons in primate caudate in reward-oriented saccadic eye movement.

Y Shimo — 2006-03-08T19:01:57-00:00

J Neurosci, Vol. 21, No. 19. (1 October 2001), pp. 7804-7814.

Recent studies have suggested that the basal ganglia are essential for reward-oriented behavior. A popular proposal is that the interaction between sensorimotor and reward-related signals occurs in the striatal projection neurons. However, the role of interneurons remains unclear. Using the one-direction-rewarded version of the memory-guided saccade task (1DR), we examined the activity of tonically active neurons (TANs), presumed cholinergic interneurons, in the caudate. Many TANs (73/155, 47.1%) responded, usually with a pause, to a visual cue that indicated both the saccade goal and the presence or absence of reward. For most TANs (44/73, 60.3%), the response was spatially selective (contralateral dominant), but was not modulated by the reward significance. TANs are thus distinct from caudate projection neurons, which have responses to the cue that are both spatially selective and reward contingent, and from midbrain dopamine neurons, which have cue responses that are spatially nonselective and reward contingent. TANs were nonetheless sensitive to the reward schedule: in the all-directions-rewarded version (ADR) compared with 1DR, the cue responses of TANs were smaller, less frequent, and less spatially selective. In 1DR, it would first be detected that reward is not given regularly, and this process would then promote discrimination of individual stimuli in relation to reward. We propose that TANs would contribute to the detection of the context that requires discrimination, whereas dopamine neurons would contribute to the stimulus discrimination. These features of TANs might be explained by their cytoarchitecture, namely, as large aspiny neurons.

Modulation of an afterhyperpolarization by the substantia nigra induces pauses in the tonic firing of striatal cholinergic interneurons.

JN Reynolds — 2005-10-14T16:48:44-00:00

J Neurosci, Vol. 24, No. 44. (3 November 2004), pp. 9870-9877.

Striatal cholinergic interneurons, also known as tonically active neurons (TANs), acquire a pause in firing during learning of stimulus-reward associations. This pause response to a sensory stimulus emerges after repeated pairing with a reward. The conditioned pause is dependent on dopamine from the substantia nigra, but its underlying cellular mechanism is unknown. Using in vivo intracellular recording, we found that both subthreshold and suprathreshold depolarizations in cholinergic interneurons induced a prolonged after-hyperpolarization (AHP) associated with a pause in their tonic firing. The AHP duration was dependent on the level of depolarization, whether elicited by intracellular current injection or by activation of excitatory inputs from the cortex. High-frequency stimulation of the substantia nigra induced potentiation of the cortically evoked excitation and increased the prolonged AHP after the stimulus. These findings from anesthetized animals suggest that a substantia nigra-induced AHP produces stimulus-associated firing pauses in cholinergic interneurons. This mechanism may underlie the acquisition of the pause response in TANs recorded from behaving animals during learning.

Nicotine amplifies reward-related dopamine signals in striatum.

ME Rice — 2006-02-26T18:43:36-00:00

Nat Neurosci, Vol. 7, No. 6. (June 2004), pp. 583-584.

Reward-seeking behaviors depend critically on dopamine signaling--dopamine neurons encode reward-related information by switching from tonic to phasic (burst-like) activity. Using guinea pig brain slices, we show that nicotine, like cocaine and amphetamine, acts directly in striatum where it enhances dopamine release during phasic but not tonic activity. This amplification provides a mechanism for nicotine facilitation of reward-related dopamine signals, including responses to other primary reinforcers that govern nicotine dependence in smokers.