Higher-Order Memory Schema and Conscious Experience

In the interesting and thought-provoking article Grazziano and colleagues argue for their Attention Schema Theory (AST) of consciousness. They present AST as a unification of Global Workspace Theory (GWT), Illusionism, and the Higher-Order Thought (HOT) theory. We argue it is a mistake to equate 'subjective experience,' ad related terms, with dualism. They simply denote experience. Also, as presented, AST does not accurately capture the essence of HOT for two reasons. HOT is presented as a version of strong illusionism, which it isn't, and HOT requires that one be aware of one's mental life, and postulates that his consists in a re-representation of what is occurring at at the lower-order levels. However, the authors deny that AST involves re-representing visual stimuli. We close by proposing an alternative unification: GWT and AST provide crucial accounts of how lower-order states are assembled and maintained, but higher-order theory provides the account of subjective experience

A Higher-Order Theory of Emotional Consciousness

Emotional states of consciousness, or what are typically called emotional feelings, are traditionally viewed as being innately programed in subcortical areas of the brain, and are often treated as different from cognitive states of consciousness, such as those related to the perception of external stimuli. We argue that conscious experiences, regardless of their content, arise from one system in the brain. On this view, what differs in emotional and non-emotional states is the kind of inputs that are processed by a general cortical network of cognition, a network essential for conscious experiences. Although subcortical circuits are not directly responsible for conscious feelings, they provide non-conscious inputs that coalesce with other kinds of neural signals in the cognitive assembly of conscious emotional experiences. In building the case for this proposal, we defend a modified version of what is known as the higher-order theory of consciousness

Understanding the Higher-Order Approach to Consciousness

Critics have often misunderstood the higher-order theory (HOT) of consciousness. Here we clarify its position on several issues, and distinguish it from other views such as the global The higher-order theory (HOT) of consciousness has often been misunderstood by critics. Here we clarify its position on several issues, and distinguish it from other views such as the global workspace theory (GWT) and early sensory models (e.g. first-order local recurrency theories). For example, HOT has been criticized for over-intellectualizing consciousness. We show that while higher-order states are cognitively assembled, the requirements are actually considerably less than often presumed. In this sense HOT may be viewed as an intermediate position between GWT and early sensory views. Also, we clarify that most proponents of HOT do not stipulate consciousness as equivalent to metacognition or confidence. Further, compared to other existing theories, HOT can arguably account better for complex everyday experiences, such as of emotions and episodic memories. This makes HOT particularly useful as a framework for conceptualizing pathological mental states

Ultrastructural Characterization of Noradrenergic Axons and Beta-Adrenergic Receptors in the Lateral Nucleus of the Amygdala

Norepinephrine (NE) is thought to play a key role in fear and anxiety, but its role in amygdala-dependent Pavlovian fear conditioning, a major model for understanding the neural basis of fear, is poorly understood. The lateral nucleus of the amygdala (LA) is a critical brain region for fear learning and regulating the effects of stress on memory. To understand better the cellular mechanisms of NE and its adrenergic receptors in the LA, we used antibodies directed against dopamine beta-hydroxylase (DβH), the synthetic enzyme for NE, or against two different isoforms of the beta-adrenergic receptors (βARs), one that predominately recognizes neurons (βAR 248) and the other astrocytes (βAR 404), to characterize the microenvironments of DβH and βAR. By electron microscopy, most DβH terminals did not make synapses, but when they did, they formed both asymmetric and symmetric synapses. By light microscopy, βARs were present in both neurons and astrocytes. Confocal microscopy revealed that both excitatory and inhibitory neurons express βAR248. By electron microscopy, βAR 248 was present in neuronal cell bodies, dendritic shafts and spines, and some axon terminals and astrocytes. When in dendrites and spines, βAR 248 was frequently concentrated along plasma membranes and at post-synaptic densities of asymmetric (excitatory) synapses. βAR 404 was expressed predominately in astrocytic cell bodies and processes. These astrocytic processes were frequently interposed between unlabeled terminals or ensheathed asymmetric synapses. Our findings provide a morphological basis for understanding ways in which NE may modulate transmission by acting via synaptic or non-synaptic mechanisms in the LA

Beta-Adrenergic Receptors in the Lateral Nucleus of the Amygdala Contribute to the Acquisition but Not the Consolidation of Auditory Fear Conditioning

Beta-adrenergic receptors (βARs) have long been associated with fear disorders and with learning and memory. However, the contribution of these receptors to Pavlovian fear conditioning, a leading behavioral model for studying fear learning and memory, is still poorly understood. The aim of this study was to investigate the involvement of βAR activation in the acquisition, consolidation and expression of fear conditioning. We focused on manipulations of βARs in the lateral nucleus of the amygdala (LA) because of the well-established contribution of this area to fear conditioning. Specifically, we tested the effects of intra-LA microinfusions of the βAR antagonist, propranolol, on learning and memory for auditory Pavlovian fear conditioning in rats. Pre-training propranolol infusions disrupted the initial acquisition, short-term memory (STM), and long-term memory (LTM) for fear conditioning, but infusions immediately after training had no effect. Further, infusion of propranolol prior to testing fear responses did not affect fear memory expression. These findings indicate that amygdala βARs are important for the acquisition but not the consolidation of fear conditioning

GABAC Receptors in the Lateral Amygdala: A Possible Novel Target for the Treatment of Fear and Anxiety Disorders?

Activation of GABAARs in the lateral nucleus of the amygdala (LA), a key site of plasticity underlying fear learning, impairs fear learning. The role of GABACRs in the LA and other brain areas is poorly understood. GABACRs could be an important novel target for pharmacological treatments of anxiety-related disorders since, unlike GABAARs, GABACRs do not desensitize. To detect functional GABACRs in the LA we performed whole cell patch clamp recordings in vitro. We found that GABAARs and GABABRs blockade lead to a reduction of evoked inhibition and an increase increment of excitation, but activation of GABACRs caused elevations of evoked excitation, while blocking GABACRs reduced evoked excitation. Based on this evidence we tested whether GABACRs in LA contribute to fear learning in vivo. It is established that activation of GABAARs leads to blockage of fear learning. Application of GABAC drugs had a very different effect; fear learning was enhanced by activating and attenuated by blocking GABACRs in the LA. Our results suggest that GABAC and GABAARs play opposing roles in modulation of associative plasticity in LA neurons of rats. This novel role of GABACRs furthers our understanding of GABA receptors in fear memory acquisition and storage and suggests a possible novel target for the treatment of fear and anxiety disorders

Hebbian Reverberations in Emotional Memory Micro Circuits

The study of memory in most behavioral paradigms, including emotional memory paradigms, has focused on the feed forward components that underlie Hebb's first postulate, associative synaptic plasticity. Hebb's second postulate argues that activated ensembles of neurons reverberate in order to provide temporal coordination of different neural signals, and thereby facilitate coincidence detection. Recent evidence from our groups has suggested that the lateral amygdala (LA) contains recurrent microcircuits and that these may reverberate. Additionally this reverberant activity is precisely timed with latencies that would facilitate coincidence detection between cortical and sub cortical afferents to the LA. Thus, recent data at the microcircuit level in the amygdala provide some physiological evidence in support of the second Hebbian postulate

The role of the lateral amygdala in the retrieval and maintenance of fear-memories formed by repeated probabilistic reinforcement

The lateral nucleus of the amygdala (LA) is a key element in the neural circuit subserving Pavlovian fear-conditioning, an animal model of fear and anxiety. Most studies have focused on the role of the LA in fear acquisition and extinction, i.e., how neural plasticity results from changing contingencies between a neutral conditioned stimulus (CS) (e.g., a tone) and an aversive unconditioned stimulus (US) (e.g., a shock). However, outside of the lab, fear-memories are often the result of repeated and unpredictable experiences. Examples include domestic violence, child abuse or combat. To better understand the role of the LA in the expression of fear resulting from repeated and uncertain reinforcement, rats experienced a 30% partial reinforcement (PR) fear-conditioning schedule four days a week for four weeks. Rats reached asymptotic levels of conditioned-fear expression after the first week. We then manipulated LA activity with drug (or vehicle) (VEH) infusions once a week, for the next three weeks, before the training session. LA infusions of muscimol (MUSC), a GABA-A agonist that inhibits neural activity, reduced CS evoked fear-behavior to pre-conditioning levels. LA infusions of pentagastrin (PENT), a cholecystokinin-2 (CCK) agonist that increases neural excitability, resulted in CS-evoked fear-behavior that continued past the offset of the CS. This suggests that neural activity in the LA is required for the retrieval of fear memories that stem from repeated and uncertain reinforcement, and that CCK signaling in the LA plays a role in the recovery from fear after the removal of the fear-evoking stimulus

Regulation of the Fear Network by Mediators of Stress: Norepinephrine Alters the Balance between Cortical and Subcortical Afferent Excitation of the Lateral Amygdala

Pavlovian auditory fear conditioning involves the integration of information about an acoustic conditioned stimulus (CS) and an aversive unconditioned stimulus in the lateral nucleus of the amygdala (LA). The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE), regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased toward the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance toward the faster but more primitive subcortical input