109 年 國立政治大學神經科學研究所（原：生命科學研究所）《生理學》

核心觀念
Wernicke 区位於顳葉左側的上顳回，屬於語言理解（語意）區。損傷會造成語意失語（Wernicke's aphasia），患者能流利說話但語意不通，且難以理解他人語言。

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解題過程

1. 辨識選項所測的腦區功能
   • (A) 辨識臉孔 → 主要涉及枕葉（顏面識別）及右側顳葉的枕顳結合區（Fusiform face area），與 Wernicke 区無關。
   • (B) 理解語言 → 正是 Wernicke 区的主要功能：語意理解。
   • (C) 協調運動 → 與小腦或頂葉/額葉運動區有關，非語言區。

核心觀念
本題在測驗 REM (Rapid Eye Movement) 期的生理特徵。REM 睡眠的關鍵特點包括：

1. 夢境常發生。
2. 大腦皮層電位呈低振幅、高頻率，與清醒時的 beta wave 相似。
3. 男性陰莖勃起（女性亦會有陰蒂充血）是常見的自律神經現象。
4. 由於 肌肉張力消失（atonia），身體基本上無自發性大幅運動，僅有眼球快速移動。

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解題步驟

(a) Dreaming（做夢）

• 研究指出 REM 期是「快速眼動」與「夢境最活躍」的階段。
• 因此「dreaming」會在 REM 期出現，排除選項 (A)。

(b) Beta wave of EEG（β 波）

• EEG 在 REM 期呈現低振幅、混合頻率的快速波形，與清醒時的 β 波相似。
• 雖然名稱上常說「低電壓混合波」，但實際頻率範圍包含 β 波(13–30 Hz)。
• 故「beta wave」會在 REM 期觀測到，排除選項 (B)。

核心觀念
本題測驗的是「快感（euphoria）」與哪一種神經傳導系統最相關。快感主要由中腦腹側被蓋區（ventral tegmental area, VTA）→腹側紋狀體（nucleus accumbens）的多巴胺多巴胺能（dopaminergic）迴路所調控，亦即多巴胺系統的活化會產生愉悅感。

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解題過程

1. 辨識選項所屬的神經遞質與功能
   • Norepinephrine（去甲腎上腺素）：主要在警覺性、注意力、壓力反應與交感神經活化上扮演角色，較少與快感直接相關。
   • Acetylcholine（乙醯膽鹼）：涉及記憶、學習與肌肉收縮，並非快感的主要介質。
   • Dopamine（多巴胺）：位於獎勵系統核心，刺激 VTA‑NAcc 迴路時可產生欣快感、動機增強與正向增強。

核心觀念
本題測驗大腦各葉的功能分工，特別是哪一個葉主要負責運動資訊的處理與產生。在神經解剖學上，額葉（Frontal lobe）內的運動皮質（primary motor cortex）是主要的運動指令中心。

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解題過程

1. 回顧大腦各葉的主要功能
   • 額葉 (Frontal lobe)：包含前額葉皮質、運動前皮質與一次運動皮質（primary motor cortex, 位於中央溝前方），主管自願運動的計畫、執行與調控。
   • 顳葉 (Temporal lobe)：以聽覺處理、語言理解與記憶儲存為主，與運動資訊無直接關聯。
   • 枕葉 (Occipital lobe)：視覺訊號的主要接收與分析區，功能限定於視覺處理。
   • 頂葉 (Parietal lobe)：負責體感 (somatosensory) 與空間定位，主要整合感覺訊息，雖與運動協調有關，但不是原始的運動指令產生處。

核心觀念
下視丘—腦垂體—腎上腺（HPA）軸是人體對外在或內在壓力（stress）的主要內分泌調節回路，透過釋放皮質醇等糖質皮質激素來協調代謝、免疫與神經行為的應對。

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解題流程

(a) 先辨識選項與 HPA 軸的主要功能

選項	內容	與 HPA 軸的關係
(A) Circadian rhythm	生理時鐘的日夜節律	雖然皮質醇呈現日夜變化，但這是 HPA 軸受下視丘視交叉上核（SCN）調控的 次要 作用，非其最主要功能。
(B) Stress	壓力反應	HPA 軸的核心功能，即在急性或慢性壓力下啟動 CRH → ACTH → 皮質醇的分泌路徑，調節能量供應、免疫抑制與情緒反應。
(C) Reproduction	生殖功能	主要受下視丘‑性腺軸（HPG）調控，與 HPA 軸僅在壓力抑制生殖時有交互作用，非主要功能。
(D) Insomnia	失眠	失眠可因皮質醇分泌異常而發生，屬 結果 而非 HPA 軸的主要目的。
(E) Chronic pain	慢性疼痛	痛覺與 HPA 軸亦有交互，但同樣屬次要或伴隨效應。

核心觀念
NMDA 受體屬於離子型（ionotropic）谷氨酸受體，結構是一個以 Mg²⁺ 為電壓依賴阻塞物的陽離子通道。它直接形成離子通道，而非藉由 G‑蛋白偶聯的第二訊息傳導路徑（metabotropic）。

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解題過程

1. 判斷「glutamate receptor」是否成立

   • NMDA 受體的配體是 L‑glutamate（亦可被 glycine/serine 作為共激活分子），屬於谷氨酸受體家族。
   • 因此選項 (A) glutamate receptor 為真。

2. 判斷「cation channel」是否成立

   • NMDA 受體的通道允許 Na⁺、K⁺ 以及 Ca²⁺ 進入細胞，屬於陽離子（cation）通道。
   • 故選項 (B) cation channel 為真。

3. 判斷「metabotropic receptor」是否成立

   • 離子型受體（如 NMDA、AMPA、kainate）直接形成離子通道；

核心觀念
此題測驗的是神經元軸突（axon）的結構與功能，特別是軸突的數量、起始部位（axon hillock）內的細胞器分布、節點（Node of Ranvier）上離子通道的分布，以及髓鞘對傳導速度的影響。要能辨識每一個描述是否符合神經解剖與生理常識。

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(a) A neuron usually has many axons.

說明：在大多數神經元中，僅有一條軸突（單極或多極神經元的「主」軸突），從細胞體（soma）延伸至遠端的目標細胞。雖然神經元可能有多支樹突（dendrites），但軸突數目幾乎都是唯一的，例外情況如某些特化的神經元可有兩條軸突，但這極少。
判斷：此敘述錯誤。

(b) The axon hillock contains many Golgi apparatus.

說明：axon hillock（軸丘）是位於細胞體與軸突交接處的區域，主要功能是產生動作電位的起點，因為此處鈉、鉀離子通道密集。它的細胞質主要富含微管與微絲，供軸突的快速運輸使用，**高爾基體（Golgi apparatus）**則多集中在細胞體的粗面內質網附近，以進行蛋白質的加工與分泌。axon hillock 本身不特別富含高爾基體。
判斷：此敘述錯誤。

核心觀念
本題測驗的是「神經傳遞物質的失活機制」之分別：

• 肽類神經傳遞物質（如 substance P、vasopressin）在釋放後主要以 肽酶（peptidases） 水解失活。
• 其他類別（胺類、氣體、氨基酸）則分別由 單胺氧化酶、氧化酶、再攝取與轉運體 等機制失活，與肽酶無關。

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解題步驟

1. 辨識選項中各神經傳遞物質的化學類別
   • histamine：胺類（單胺） → 主要由 單胺氧化酶 (MAO) 代謝。
   • nitric oxide (NO)：氣體分子 → 以 氧化 形式迅速失活，非肽酶作用。
   • substance P：肽（神經肽） → 受 肽酶 (peptidases) 水解。
   • vasopressin：肽（抗利尿激素） → 同樣由 肽酶 分解。
   • acetylcholine：膽鹼類 → 由 膽鹼酯酶 (acetylcholinesterase) 水解，屬於酯酶而非肽酶。

核心觀念
海馬迴是形成與鞏固近期情景記憶（episodic memory）的關鍵結構，雙側受損會造成順行性失憶（anterograde amnesia），使新資訊無法有效編碼成長期記憶；已存於大腦皮質的遙遠記憶則相對保留，且海馬迴並非工作記憶或情緒調節的主要中樞。

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解題過程

選項	評估說明	結論
(A) loss of remote memories	遙遠記憶（remote memories）在形成之後已被轉移至新皮層（neocortex），海馬迴損傷不會抹除這些已鞏固的記憶。	錯
(B) loss of working memory	工作記憶主要由前額葉皮層（prefrontal cortex）維持，海馬迴的功能與之無關。	錯

核心觀念
本題考查對阿茲海默症（Alzheimer's disease, AD）流行病學與病理特徵的基本認識，尤其是疾病年齡分布、發病型態、臨床表現以及大腦病理變化（senile plaques）。

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(a) 各選項之判斷與說明

(A) AD only occurs in people older than 60 years of age.

• 阿茲海默症雖以老年人為主，但​早發性阿茲海默症（early‑onset AD）亦可在 30‒60 歲出現，尤其與 APP、PSEN1、PSEN2 等基因突變相關。
• 因此「僅在 60 歲以上」的說法過於絕對，屬不正確。

(B) Most AD cases are sporadic.

• 大約 90‑95% 為散發（sporadic）型，只有少數（5‑10%）為家族遺傳型。此敘述符合流行病學資料，正確。

核心概念
本題測驗的是長期增強 (Long‑Term Potentiation, LTP) 的基本特性：它是突觸可塑性的主要形式，與學習、記憶相關，透過增強突觸傳遞效能而非改變神經動作電位的幅度。

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(a) 為何要先釐清 LTP 的定義？

LTP 指在高頻刺激後，突觸後膜的興奮性突觸後電位 (EPSP) 持續增大，形成長期的突觸強化。其主要機制包括：

• NMDA 受體活化 → Ca²⁺流入 → 激活 CaMKII、PKA 等訊號通路。
• AMPA 受體數量或導通性提升 → EPSP 振幅增大。
• 突觸結構重塑（如樹突棘增大）亦可增強傳遞。

重要的是，LTP 影響的是突觸傳遞效率，而非單一神經元產生的動作電位（AP）幅度。

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(b) 各選項的正誤判斷

選項	內容	判斷依據	正確性

核心觀念
本題測驗的是酒精代謝與致癌機制之間的關聯，特別是**乙醛脫氫酶 2（ALDH2）**的功能缺失會使體內致癌的乙醛累積，進而提高癌症風險。

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解題過程

1. 酒精在人體的代謝路徑

   • 飲酒後，**酒精脫氫酶（ADH）**把乙醇（EtOH）氧化成乙醛（acetaldehyde）。
   • 乙醛是一個高度活性的代謝產物，具有致突變、致癌的特性。
   • 正常情況下，**乙醛脫氫酶（ALDH）**會迅速將乙醛進一步氧化成較無害的乙酸（acetate），再進入三羧酸循環代謝。

2. 酶的種類與編號

   • 目前已知的兩大類酒精代謝相關酶：
     • 酒精脫氫酶（ADH）：主要將乙醇變成乙醛。
     • 乙醛脫氫酶（ALDH）：將乙醛轉為乙酸。
   • 在人類中，ALDH2 是線粒體內最重要的乙醛脫氫酶，負責大部分乙醛的清除。

3. ALDH2 基因缺陷與致癌風險

   • 東亞人群（包括台灣）中常見 ALDH2*2（rs671） 基因變異，使酶活性顯著下降（約10%~30% of normal）

核心觀念

本題考察下視丘在性行為與性取向調控中的角色。下視丘除了維持體溫、食慾、睡眠與內分泌恆定，也參與生殖行為、性動機及性別相關行為的神經調控。

前下視丘（anterior hypothalamus）內含若干與性別差異及性行為相關的神經核團，其中人類的前下視丘間質核第 3 部（第三間質核，$INAH\text{-}3$）曾被研究與性取向及性別差異相關。因此，在本題選項中，最符合題意的是 anterior hypothalamus。

解題方法

判斷此題可從「腦區功能」切入：

1. 先辨認各選項所屬的神經系統位置。
2. 找出與性行為、性動機及生殖內分泌調控直接相關的腦區。
3. 下視丘是連結神經系統與內分泌系統、調節生殖功能的重要中樞，因此前下視丘符合題意。

性取向不是由單一腦區獨立決定，而是與遺傳、胚胎期荷爾蒙、神經發育及多個腦區共同相關。本題以傳統生理學與神經科學考點而言，將答案指向前下視丘相關核團。

選項分析

(A) corpus callosum：胼胝體

胼胝體是連接左右大腦半球的主要白質纖維束，負責兩側大腦皮質之間的資訊傳遞與整合。

它並非主要負責性行為、性動機或生殖內分泌調控的腦區，因此不是本題答案。

(B) superchiasmatic nucleus：視交叉上核

題目中的 superchiasmatic nucleus 通常是指 suprachiasmatic nucleus，視交叉上核。

核心觀念
本題測驗對胰島素（insulin）的主要代謝作用的認知：胰島素是促進組織攝取養分、儲存能量、抑制分解的荷爾蒙。重點在於辨識哪些生理反應是 胰島素直接或間接誘發，哪些則與胰島素無關或相反。

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解題步驟

選項	內容	與胰島素作用的符合度	為何
(A)	enhancing amino acid uptake by skeletal muscle（促進骨骼肌對胺基酸的攝取）	符合	胰島素刺激肌肉細胞的蛋白質合成，能上調胺基酸轉運子（例如系統 A、系統 L）以及 mTOR 路徑，使胺基酸有效進入肌肉細胞。
(B)	activating glucose reabsorption in the kidney（活化腎臟葡萄糖再吸收）	不符合	腎臟的葡萄糖再吸收主要由 SGLT2/1 完成，受血糖濃度和腎小管壓力調控，胰島素不直接調節此過程。
(C)	promoting glucose transport in skeletal muscle, red blood cells and the brain（促進骨骼肌、紅血球與大腦的葡萄糖運輸）	部分正確、整體錯誤	- 骨骼肌：胰島素透過 GLUT4 誘發葡萄糖攝取，符合。<br>- 紅血球與大腦：主要依賴 GLUT1 與 GLUT3，不受胰島素調節，因此此選項的敘述過度廣泛而不正確。

核心概念
此題測驗考生對「腦部疾病常見的神經傳遞物質失調」的認識。

• 抑鬱症（depression）主要與 血清素（serotonin） 的缺乏或活性下降有關。
• 癲癇發作（seizure）則多與 γ‑氨基丁酸（GABA） 的抑制作用減弱（或興奮性谷氨酸（glutamate）過度活化）相關。

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解題過程

1. 辨識抑鬱症的關鍵神經傳遞物質

   • 抑鬱症的「單胺假說」指出，血清素（5‑HT）、去甲腎上腺素（NE） 與 多巴胺（DA） 的供應不足會導致情緒低落、快感缺失等症狀。臨床常用 SSRI（Selective Serotonin Reuptake Inhibitor） 增加 5‑HT 可改善症狀，故血清素被視為抑鬱的主要失調神經傳導。
   • 因此在本題的配對中，抑鬱症應選 serotonin。

2. 辨識癲癇發作的關鍵神經傳遞物質

   • 正常大腦的興奮–抑制平衡是由 興奮性谷氨酸（glutamate） 與 抑制性 GABA 維持。

The blood-brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system (CNS) where neurons reside. It is formed by specialized capillaries in the brain that have tight junctions between endothelial cells, a thick basement membrane, and are surrounded by astrocytes and pericytes.

Function: The BBB protects the brain from potentially harmful substances circulating in the blood, such as toxins, pathogens, and fluctuations in ion concentrations. It maintains a stable environment for neuronal function, crucial for proper brain activity. It also controls the passage of essential nutrients (like glucose and amino acids) and oxygen into the brain, and the removal of waste products.

Structure: The BBB is characterized by:

1. Tight junctions: Endothelial cells lining brain capillaries are fused together by extensiv

The gut-brain axis is a bidirectional communication system that links the central nervous system (CNS) and the enteric nervous system (ENS) of the gastrointestinal tract. This complex network involves neural, endocrine, immune, and metabolic pathways.

Communication Pathways:

1. Neural Pathways: The vagus nerve is a major pathway for direct neural communication between the gut and the brain. The ENS also communicates with the CNS through spinal nerves.
2. Endocrine Pathways: Gut hormones (e.g., ghrelin, leptin, GLP-1) produced by enteroendocrine cells can enter the bloodstream and act on the brain to influence appetite, mood, and behavior.
3. Immune Pathways: The gut houses a large population of immune cells. Gut microbiota can influence immune responses, and inflammatory mediators produced in the gut can signal to the brain, impacting mood and behavior.

Synaptic pruning is a fundamental neurodevelopmental process by which excess synapses (connections between neurons) are eliminated. This process begins in early childhood and continues through adolescence and into early adulthood. It is driven by experience and activity-dependent mechanisms, where synapses that are frequently used are strengthened, while those that are less used or redundant are eliminated.

Mechanism: Synaptic pruning is thought to be mediated by several factors, including:

1. Activity-dependent mechanisms: Neurons that fire together, wire together (Hebb's rule). Synapses that receive strong and frequent stimulation are stabilized and strengthened, while those that receive weak or infrequent stimulation are pruned.
2. Microglial involvement: Microglia, the resident immune cells of the brain, play an active role in synaptic pruning by engulfing and removing synapses.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the motor system. It is characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta, a region in the midbrain that plays a crucial role in controlling movement.

Key Features:

1. Motor Symptoms: The cardinal motor symptoms of PD are:
   • Tremor: Often a resting tremor, typically starting in one limb and characterized by a "pill-rolling" motion.
   • Rigidity: Stiffness and resistance to passive movement of the limbs and trunk.
   • Bradykinesia: Slowness of movement, which is a hallmark symptom and affects voluntary actions.
   • Postural instability: Impaired balance and coordination, leading to a tendency to fall.

Here's a description of an action potential and its phases, which can be used to draw and label the graph.

Drawing the Action Potential:
You would draw a graph with time on the x-axis and membrane potential (in millivolts, mV) on the y-axis. The y-axis should range from approximately -90 mV to +40 mV.

Phases and Key Voltages:

• (a) Resting Membrane Potential (RMP): This is the baseline potential of the neuron when it is not actively transmitting a signal. It is typically around -70 mV in most neurons. This is maintained primarily by the sodium-potassium pump and the differential permeability of the membrane to potassium ions.

• (b) Threshold Potential: This is the critical level of membrane depolarization that must be reached to trigger an action potential. If the membrane potential reaches the threshold, an action potential will fire. The threshold is typically around -55 mV.

• (c) Phase of Depolarization: This is the rapid rising phase of the action potential. The membrane potential becomes less negative and then positive. It is caused by the rapid influx of sodium ions ($Na^+$) into the neuron. The potential rises from the threshold to a peak of about +30 mV to +40 mV.

• (d) Phase of Hyperpolarization (Repolarization and Undershoot):

  • Repolarization: After reaching the peak, the membrane potential rapidly returns to negative values. This is caused by the inactivation of voltage-gated sodium channels and the opening of voltage-gated potassium channels ($K^+$ channels), allowing $K^+$ ions to flow out of the neuron.
  • Hyperpolarization (Undershoot): The membrane potential briefly becomes more negative than the resting membrane potential (e.g., -75 mV to -80 mV). This occurs because the voltage-gated potassium channels close more slowly than the sodium channels.

Ionic Flows and Channels/Membrane Proteins Activated:

1. Resting Membrane Potential (-70 mV):

   • Ionic Flow: Primarily outward movement of $K^+$ ions through leak channels and some inward leak of $Na^+$ ions. The Na+/K+-ATPase pump actively transports 3 $Na^+$ out for every 2 $K^+$ in, maintaining the concentration gradients.
   • Channels/Proteins: $K^+$ leak channels, $Na^+$ leak channels, Na+/K+-ATPase pump.

2. Stimulus and Reaching Threshold (-70 mV to -55 mV):

   • Ionic Flow: A stimulus causes a small influx of $Na^+$ ions through ligand-gated or mechanically-gated channels, leading to depolarization.
   • Channels/Proteins: Ligand-gated or mechanically-gated ion channels.

Hormones are chemical messengers produced by endocrine glands that travel through the bloodstream to target cells and bind to specific receptors, thereby regulating various physiological functions. Here's an example illustrating this process using insulin:

Hormone: Insulin
Source: Beta cells of the islets of Langerhans in the pancreas.
Target Cells: Primarily liver cells (hepatocytes), skeletal muscle cells, and adipose tissue cells (adipocytes). Also affects other cells to a lesser extent.
Receptor Type: Insulin receptor, which is a receptor tyrosine kinase (RTK).

Physiological Function Affected: Regulation of blood glucose levels and cellular energy metabolism.

Mechanism of Action:

1. Binding to Receptor: After a meal, when blood glucose levels rise, the pancreas releases insulin. Insulin travels through the bloodstream and reaches its target cells. At the target cell surface, insulin binds to the extracellular alpha subunits of the insulin receptor.

2. Receptor Activation: Insulin binding causes a conformational change in the insulin receptor. This leads to the autophosphorylation of the intracellular beta subunits of the receptor, activating its tyrosine kinase activity.

3. Signal Transduction Cascade: The activated insulin receptor then phosphorylates various intracellular proteins, initiating a signaling cascade. Key downstream signaling molecules include insulin receptor substrates (IRS proteins), which are then phosphorylated by the receptor.

4. Activation of Key Pathways: Phosphorylated IRS proteins activate multiple intracellular signaling pathways, most notably:

   • PI3K/Akt pathway: This pathway is crucial for promoting glucose uptake and metabolism. Activation of the PI3K/Akt pathway leads to:

Calcium ions ($Ca^{2+}$) play a pivotal role in initiating muscle contraction in both smooth and skeletal muscles, but the mechanisms by which they act differ significantly.

Calcium's Role in Muscle Contraction:
In both muscle types, an increase in intracellular $Ca^{2+}$ concentration is the trigger for contraction. This increase typically occurs in response to a neural stimulus. The $Ca^{2+}$ ions then bind to specific proteins, leading to the interaction of actin and myosin filaments, which generates force and shortens the muscle fiber.

1. Skeletal Muscle Contraction:

• Source of Calcium: $Ca^{2+}$ is stored in the sarcoplasmic reticulum (SR), a specialized endoplasmic reticulum in muscle cells.
• Trigger: A motor neuron releases acetylcholine (ACh) at the neuromuscular junction. ACh binds to receptors on the sarcolemma, causing depolarization and triggering an action potential. This action potential propagates along the sarcolemma and down the T-tubules (transverse tubules).
• Calcium Release: The action potential traveling down the T-tubules causes a conformational change in dihydropyridine receptors (DHPRs) (voltage sensors) located in the T-tubule membrane. These DHPRs are physically coupled to ryanodine receptors (RyRs) on the SR membrane. This coupling triggers the opening of RyRs, leading to a rapid release of $Ca^{2+}$ from the SR into the sarcoplasm (cytosol).
• Regulatory Proteins: In skeletal muscle, the thin filaments (actin) are associated with two regulatory proteins: troponin and tropomyosin.
  • In the resting state, tropomyosin blocks the myosin-binding sites on actin.
  • When $Ca^{2+}$ concentration increases, $Ca^{2+}$ binds to the troponin C (TnC) subunit of troponin.
  • This binding causes a conformational change in troponin, which in turn moves tropomyosin away from the myosin-binding sites on actin.
• Cross-bridge Cycling: With the myosin-binding sites exposed, myosin heads can bind to actin, forming cross-bridges. The subsequent cycling of myosin heads (binding, pivoting, detaching, re-cocking) powered by ATP hydrolysis leads to the sliding of actin filaments past myosin filaments, resulting in muscle shortening (contraction).
• Relaxation: Contraction ceases when $Ca^{2+}$ is removed from the sarcoplasm by the sarco/endoplasmic reticulum $Ca^{2+}$-ATPase (SERCA) pump, which actively transports $Ca^{2+}$ back into the SR. This allows tropomyosin to re-block the myosin-binding sites.

2. Smooth Muscle Contraction:

• Source of Calcium: $Ca^{2+}$ comes from both the sarcoplasmic reticulum (SR) and, importantly, from extracellular fluid entering the cell through voltage-gated or receptor-operated calcium channels in the cell membrane.
• Trigger: Smooth muscle contraction can be triggered by various stimuli, including neurotransmitters, hormones, mechanical stretch, and changes in membrane potential.
• Calcium Release/Influx: When stimulated, $Ca^{2+}$ is released from the SR and also enters the cell from the extracellular space.
• Regulatory Protein: Smooth muscle lacks troponin. Instead, it uses calmodulin, a calcium-binding protein.
  • When intracellular $Ca^{2+}$ concentration increases, $Ca^{2+}$ binds to calmodulin.