Response characteristics of basolateral and centromedial neurons in the primate amygdala

“…loops converging in the amygdala suggests that the basolateral nuclei are primarily involved in evaluating the emotional content of sensory inputs, whereas the centromedial nuclei generate an enhanced level of attention and arousal necessary for improved signal detection (Davis and Whalen, 2001).”

“As predicted by Whalen et al. (1998), the amygdala might allocate increased resources to process images with ambiguous or uncertain content.”

“This proposal has been confirmed experimentally in multiple species under multiple ex- perimental conditions (Critchley et al., 2001; Hsu et al., 2005; Herry et al., 2007; Platt and Huettel, 2008).”

“As a manifestation of its role in assessing the relevance/significance of stimuli, the amygdala is involved in allocating attention to stimuli of importance (Holland and Gallagher, 1999; Adolphs et al., 2005; Roesch et al., 2010).”

“The basolateral nuclei receive highly processed sensory information from the neocortex of temporal and parietal areas and project back to all sensory and association areas (with the exception of the frontal pole and primary motor cortex) (McDonald, 1998; Stefanacci and Amaral, 2002).”

“, the insula, olfactory cortex); (3) the basolateral nuclei of the amygdala (Krettek and Price, 1978; Amaral and Price, 1984; Amaral et al., 1992).”

“, the insula, olfactory cortex); (3) the basolateral nuclei of the amygdala (Krettek and Price, 1978; Amaral and Price, 1984; Amaral et al., 1992).”

“Based on neural architecture and connectivity, the nuclei in the amygdala can be divided in two main groups (McDonald, 1992; Pape and Paré, 2010).”

“An alternative explanation for the higher propensity of the CM neurons to signal task events is the purported role of the amygdala in allocating attention to relevant stimuli (Kapp et al., 1994; Davis and Whalen 2001; Sander et al., 2003).”

“The mammalian amygdala plays an important role in detecting and learning the emotional significance of stimuli encountered by an organism (LeDoux, 2000; Paré et al., 2004).”

“S1, available at www.jneurosci.org as supplemental material) that were all localized to an area ventral to the central nucleus, at the boundary between the BL and CM nuclei, where intercalated neurons have been histologically identified (Ghashghaei and Barbas, 2002).”

“A new conceptual framework, the component process model of emotion (Sander et al., 2005), might also account for the observed response properties reported here, although it does not predict any nuclear specialization.”

“Indeed, the central nucleus has been shown to support conditioning (Killcross et al., 1997; Hall et al., 2001; Everitt et al., 2003; Wilensky et al., 2006).”

“As a manifestation of its role in assessing the relevance/significance of stimuli, the amygdala is involved in allocating attention to stimuli of importance (Holland and Gallagher, 1999; Adolphs et al., 2005; Roesch et al., 2010).”

“This proposal has been confirmed experimentally in multiple species under multiple ex- perimental conditions (Critchley et al., 2001; Hsu et al., 2005; Herry et al., 2007; Platt and Huettel, 2008).”

“…has been challenged by experiments that showed involvement of the central nucleus in stimulus-reinforcement associations (Hall et al., 2001; Wilensky et al., 2006), it nevertheless predicts that neurons in the centromedial and basolateral nuclei should respond differentially to the…”

“The connection of the CM neurons to the nucleus basalis and the bed nucleus of the stria terminalis (Jones et al., 1976) might explain how increased activity in the central nucleus translates into increased attention and vigilance (Dringenberg and Vanderwolf, 1996).”

“The main classes of neurons in each nucleus of the amygdala have been characterized in great detail in rodents and cats (McDonald, 1992; Lambertz et al., 1995; Pape, 2005; Sosulina et al., 2006; Herry et al., 2007), but given species-specific differences (Pitkanen and Amaral, 1991; McDonald and Augustine, 1993) and th…”

“…this functional dichotomy has been challenged by experiments that showed involvement of the central nucleus in stimulus-reinforcement associations (Hall et al., 2001; Wilensky et al., 2006), it nevertheless predicts that neurons in the centromedial and basolateral nuclei should respond…”

“In monkeys, Belova et al. (2007) have shown that fix-spot responses can be regarded as the earliest predictors of reward.”

“The basolateral nuclei receive highly processed sensory information from the neocortex of temporal and parietal areas and project back to all sensory and association areas (with the exception of the frontal pole and primary motor cortex) (McDonald, 1998; Stefanacci and Amaral, 2002).”

“During recordings, the ring was secured into a rigid frame (for details, see Gothard et al., 2007).”

“These cells, previously documented in the cat amygdala (Paré and Gaudreau, 1996), are discovered only if they are selective for one of the images in the stimulus set.”

“…Lambertz et al., 1995; Pape, 2005; Sosulina et al., 2006; Herry et al., 2007), but given species-specific differences (Pitkanen and Amaral, 1991; McDonald and Augustine, 1993) and the differences in experimental approach, the correspondence between classes of neurons described in the current…”

“Previous single-cell recordings in the monkey and human amygdala showed the existence of amygdala neurons that are highly selective for categories of images (faces) as well as for exemplars from a category (Gothard et al., 2007; Mormann et al., 2008; Viskontas et al., 2009).”

“(Kaada, 1951; Kapp et al., 1982; Pascoe and Kapp, 1985; Reis and Ledoux, 1987; Laine et al., 2009).”

“This proposal has been confirmed experimentally in multiple species under multiple ex- perimental conditions (Critchley et al., 2001; Hsu et al., 2005; Herry et al., 2007; Platt and Huettel, 2008).”

“The stimuli consisted of monkey faces, extracted from an extended library of digitized images of monkey facial expressions (Gothard et al., 2004) and other images that included human faces, random objects, landscapes, animals, food items, and abstract images.”

“Indeed, electrical stimulation of the central nucleus increases attention and orienting (Gallagher et al., 1990; Kapp et al., 1994) by activating the cholinergic neurons in the basal forebrain.”

“As a manifestation of its role in assessing the relevance/significance of stimuli, the amygdala is involved in allocating attention to stimuli of importance (Holland and Gallagher, 1999; Adolphs et al., 2005; Roesch et al., 2010).”

“The electrodes emerged from the cannulae and were advanced into the brain by precision motors that tensed or relaxed a rubber tube attached to the back of the electrode (Mountcastle et al., 1991; Eckhorn and Thomas, 1993).”

“Previous single-cell recordings in the monkey and human amygdala showed the existence of amygdala neurons that are highly selective for categories of images (faces) as well as for exemplars from a category (Gothard et al., 2007; Mormann et al., 2008; Viskontas et al., 2009).”

“The presence of electrically coupled networks of interneurons (Muller et al., 2005) could mediate precisely timed switches in the convergent but complementary inputs at the level of the recorded neurons.”

“(Kaada, 1951; Kapp et al., 1982; Pascoe and Kapp, 1985; Reis and Ledoux, 1987; Laine et al., 2009).”

“The electrodes emerged from the cannulae and were advanced into the brain by precision motors that tensed or relaxed a rubber tube attached to the back of the electrode (Mountcastle et al., 1991; Eckhorn and Thomas, 1993).”

“Given the rarity of these neurons and their low, regular firing rates, they may belong to a subclass of cholinergic intercalated neurons (Nitecka and Frotscher, 1989).”

“, 1976) might explain how increased activity in the central nucleus translates into increased attention and vigilance (Dringenberg and Vanderwolf, 1996).”

“The main classes of neurons in each nucleus of the amygdala have been characterized in great detail in rodents and cats (McDonald, 1992; Lambertz et al., 1995; Pape, 2005; Sosulina et al., 2006; Herry et al., 2007), but given species-specific differences (Pitkanen and Amaral, 1991; McDonald and Augustine, 1993) and th…”

“This latter observation replicates findings from the rodent amygdala, where a large proportion of the neurons in the central nucleus show sustained, high-rate activity (Dumont et al., 2002).”

“…and cats (McDonald, 1992; Lambertz et al., 1995; Pape, 2005; Sosulina et al., 2006; Herry et al., 2007), but given species-specific differences (Pitkanen and Amaral, 1991; McDonald and Augustine, 1993) and the differences in experimental approach, the correspondence between classes of neurons…”

“(Kaada, 1951; Kapp et al., 1982; Pascoe and Kapp, 1985; Reis and Ledoux, 1987; Laine et al., 2009).”

“In the CM nuclei, the dimensionality of stimulus representation is likely to be reduced because the output of a large number of BL neurons converge onto a smaller number of CM neurons (Carlo et al. 2010).”

“The main classes of neurons in each nucleus of the amygdala have been characterized in great detail in rodents and cats (McDonald, 1992; Lambertz et al., 1995; Pape, 2005; Sosulina et al., 2006; Herry et al., 2007), but given species-specific differences (Pitkanen and Amaral, 1991; McDonald and Augustine, 1993) and th…”

“We report a small number of neurons with distinct firing properties recorded from the expected location of the intercalated neurons; however, the regular firing patterns of these neurons do not agree with the firing patterns of anatomically confirmed, GABAergic intercalated neurons in rodents (Collins and Paré, 1999).”

“The removable seal kept the dura sterile and supple and prevented the growth of scar tissue, making the use of antibiotics, daily chamber maintenance, and dura debridement unnecessary (Spitler and Gothard, 2008).”

“The main classes of neurons in each nucleus of the amygdala have been characterized in great detail in rodents and cats (McDonald, 1992; Lambertz et al., 1995; Pape, 2005; Sosulina et al., 2006; Herry et al., 2007), but given species-specific differences (Pitkanen and Amaral, 1991; McDonald and Augustine, 1993) and th…”

“In monkeys, single cell recordings found, for instance, that laterobasal neurons in the monkey amygdala responded more selectively to visual stimuli, whereas centromedial neurons responded preferentially to task cues [Mosher et al., 2010].”

“…that selectivity for the content of the images is expressed by changes in (1) the polarity of the response, i.e., inhibitory or excitatory, (2) the magnitude of the response, and (3) the temporal pattern of the response (e.g., bursting, phasic, or tonic changes in firing rate; see Figure 2 in [25]).”

“The amygdala contains cells selective for specific identities and expressions (Mosher et al., 2010), and most intriguingly, for eye contact (Zimmerman et al.”

“Combined with a resurgence of interest in similar studies in non-human primates [36, 43, 72, 73], these approaches are starting to provide circuit-level evidence for the role of the amygdala in one specific aspect of social cognition: the processing of faces.”

“The large proportion of inhibitory responses may be indicative of the dense inhibitory network within the amygdala [12].”

“The divergent effects of activation of the BLA and CeA may relate to the relatively higher basal firing rate of CeA neurons compared to BLA neurons (Mosher et al., 2010); thus, disinhibition of the CeA may have been less effective.”

“approach is particularly important for structures whereby distinct subfields or regions exhibit distinct functionality (e.g., BLA vs. CMA; Mosher et al., 2010) and promises to provide insight into circuit-level connections that can be investigated further with other imaging modalities 8 HO ET AL.”

“This function has also been demonstrated using tasks in which emotional information is prioritized and receives privileged access to consciousness and attentional resources (Vuilleumier and Schwartz, 2001).”

“This is in agreement with the observation in rabbits and primates of high-firing neurons in the centromedial nuclei (Pascoe and Kapp, 1985; Mosher et al., 2010), perhaps suggesting the existence of a population of inhibitory interneurons there, as they tend to have higher firing rates than…”

“, 1987), single cell recording (Faber et al., 2001; Mosher et al., 2010; Paré and Collins, 2000) and lesion studies (Balleine et al.”

“The AMG is also involved in modulating cognitive functions as well as behavior and has many connections to brain areas directly involved in behavioral output (Mosher et al., 2010).”

“Although initial reports overwhelmingly described reduced connectivity in ASD [Muller, 2007; Muller et al., 2011], more recent work has demonstrated that ASD is characterized by both over connectivity and under connectivity [Di Martino et al., 2014; Venkataraman, Duncan, Yang, & Pelphrey, 2015] and…”

“, 2006; Diehl and Romanski, 2014), and in the monkey amygdala, another face-vocalization integration area, where many neurons are robustly responsive to faces (Gothard et al., 2007; Kuraoka and Nakamura, 2007; Mosher et al., 2010), but fewer neurons respond to corresponding vocalizations (Kuraoka and Nakamura, 2007).”

“Nociceptive stimuli activate the central noradrenergic system in the locus ceruleus (LC) directly and also indirectly via the centromedial amygdala that allocates attention to relevant stimuli (Van Bockstaele et al., 2001; Gao et al., 2004; Mosher et al., 2010).”

“Alternatively hippocampal response specifics might also come as feedback from the amygdala, which is anatomically close and also represent facial information (Rolls 1984; Leonard et al. 1985; Gothard et al. 2007; Hoffman et al. 2007; Mosher et al. 2010; Rutishauser et al. 2011; Hadj-Bouziane et al. 2012).”

“, 2013), with different morphologic and physiologic properties (Mosher et al., 2010).”

“Primarily a sensory input region, the BL amygdala is involved in evaluating the emotional content of incoming information (Davis and Whalen, 2001; Mosher et al., 2010; Pape and Pare, 2010; Sah et al., 2003).”

“Assessment of this reconstruction method was previously found to be accurate to within (cid:2) 1 mm (Mosher et al., 2010).”

“In rodents, the MeA is a multisensory area that receives cortically-processed sensory input from visual and auditory modalities (Mosher et al., 2010).”

“Specifically, we activated within a trial neurons that respond to (1) alerting stimuli (Mosher et al., 2010), (2) broad categories of social vs. non-social stimuli (Gothard et al., 2007), (3), faces (Minxha et al., 2017; Sanghera et al., 1979), eye contact (Mosher et al., 2014), and (4)…”

“Previous findings have shown that the primate and the rodent amygdala exhibit robust excitatory as well as inhibitory responses (Belova et al., 2007; Herry et al., 2008; Mosher et al., 2010) hence our approach identifies both types.”

“, 1992; Swanson and Petrovich, 1998) and functional dissociations (Hatfield et al., 1996; Mosher et al., 2010).”

“On the other hand, a CMA-network mediates reflexive reactions to threat [30,31], and this process is modulated by the BLA.”

“We also compared decoding contributions of basolateral and centromedial amygdala neurons, as these amygdala regions differ in connectivity and function (Balleine and Killcross, 2006; Duvarci and Pare, 2014; Mosher et al., 2010; Namburi et al., 2015).”

“The CMA mediate reflexive reactions to threat together with the hypothalamus and brainstem (Mosher et al., 2010; Fox et al., 2015).”

“Recent neuroimaging and behavioral studies indicate that the amygdala appears to extract affective aspects of touch (e.g., McGlone and Reilly, 2010; Morrison et al., 2010; Lucas et al., 2015).”

“The lateral portion of amygdala was established to coordinate visual information, which was supported by a tract-tracing study (25) and single-cell recordings (26) in monkeys.”

“…and Tanaka, 1994); and amygdala, which has direct inputs from TEO (Webster et al., 1991; Stefanacci and Amaral, 2002) and is known to carry neural representations of visual stimulus–reward associations and abstract categories (such as different classes of facial expression; Mosher et al., 2010).”

“Only a few single unit studies reported an uneven distribution of neurons with particular response properties across the nuclei (e.g., Grabenhorst et al., 2019 , Grabenhorst et al., 2016 ; Mosher et al., 2010 ; Zhang et al., 2013 ).”

“…orientation toward relevant signals in the environment and alter reward conditioning [89], whereas atrophy of the basolateral nucleus might lead to disinhibition of the centrome-dial region and thus hypervigilance to threat [89–92] and impaired eye processing when viewing facial expressions [23].”

“In contrast, the BLA, with its connections to the CMA and with extensive cortical regions, is primarily involved in evaluating the emotional content of sensory inputs (Mosher et al., 2010).”

“Firing pattern properties and visual selectivity have been previously described for this dataset in (Mosher et al., 2010) and (Gothard et al.”

“…family routines, which affect sleep duration and in turn brain structure in children includes the basolateral (BLA) and centromedial amygdala (CMA) subregions, which have distinct cellular architecture and connectivity patterns (Mosher et al., 2010; Rajbhandari et al., 2017; Skelly et al., 2020).”

“Whereas previous studies had already identified these selectivity dimensions in isolation [11,36,38,113], the results of this study argue that interpreting the selectivity of neuron without testing it across other stimuli or task parameters can be easily misleading.”

“In the rest of the temporal cortex, there are many areas that respond to socially relevant stimulid especially facesdand that correlate with SNS, in both humans and macaques.”

“It can invoke emotional responses and inhibit behavior at the same time.(57) Moreover, it is involved in both formation of emotional memories with the hippocampus and”

“hippocampus, contributing to the integrity of behavior, stress and reward circuits (Mosher et al., 2010).”

“stimuli, such as faces and artifacts, have been reported in the lateral nucleus (Nishijo et al., 1988a; Nakamura et al., 1992; Mosher et al., 2010).”

“This focus on the whole amygdala contrasts with evidence from animal studies that shows differential connectivity patterns of amygdala subnuclei with the rest of the brain and that implicate these subnuclei in differential functions (Janak and Tye, 2015; Mosher et al., 2010; Schmitt et al., 2012).”

“48 LA is the largest amygdala nucleus in humans, with the highest number of neurons, 35 but the BM nucleus tends to be involved in the amygdala epi-leptogenicity of patients with mTLE as well.”

“CMA nuclei are involved in maintaining attention and vigilance as well as relaying information to brain regions involved in fear learning (Brown et al., 2014; Mosher et al., 2010).”